ascorbic-acid and Hypertension

It is suggested that supplementation of vitamin C reduces hyperglycemia and lowers blood pressure in hypertensives by enhacing the formation of prostaglandin E1 (PGE1), PGI2 (prostacyclin), endothelial nitric oxide (eNO), and restore essential fatty acid (EFA) metabolism to normal and enhance the formation of lipoxin A4 (LXA4), a potent anti-inflammatory, vasodilator and antioxidant. These actions are in addition to the ability of vitamin C to function as an antioxidant. In vitro and in vivo studies revealed that PGE1, PGI2 and NO have cytoprotective and genoprotective actions and thus, protect pancreatic β and vascular endotheilial cells from the cytotoxic actions of endogenous and exogenous toxins. AA, the precursor of LXA4 and LXA4 have potent anti-diabetic actions and their plasma tissue concentrations are decreased in those with diabetes mellitus and hypertension. Thus, vitamin C by augmenting the formation of PGE1, PGI2, eNO, LXA4 and restoring AA content to normal may function as a cytoprotective, anti-mutagenic, vasodilator and platelet anti-agregator actions that explains its benefical action in type 2 diabetes mellitus and hypertension.

Topics: Alprostadil; Ascorbic Acid; Cytoprotection; Diabetes Mellitus, Type 2; Dietary Supplements; Epoprostenol; Fatty Acids, Essential; Humans; Hyperglycemia; Hypertension; Lipoxins; Nitric Oxide; Pancreas

High sodium, high glucose, and obesity are important risk factors for age-related diseases such as cardiovascular disease (CVDs), stroke, and cancer. Coupling factor 6 (CF6) is released from vascular endothelial cells and functions as a circulating peptide that inhibits prostacyclin and nitric oxide generation by intracellular acidosis. High glucose elevates CF6 by activation of protein kinase C and p38 mitogen-activated protein kinase, whereas CF6 causes type 2 diabetes mellitus, resulting in a high glucose vicious cycle. Low glucose increases inhibitory factor peptide 1, an endogenous inhibitor of CF6. High salt intake increases CF6 through nuclear factor κB signaling, whereas CF6 induces salt-sensitive hypertension and salt-induced congestive heart failure. Oral administration of vitamin C cancels salt-induced increase in CF6, and estrogen replacement leads to the delayed onset of CF6-induced salt-sensitive hypertension and the rescue from cardiac systolic dysfunction. Because CF6 contributes to the onset of CVDs, nutritional regulation of CF6 will shed light on the understanding of preventive strategy and mechanisms for CVDs and a target for therapy.

Topics: Administration, Oral; Ascorbic Acid; Diabetes Mellitus, Type 2; Endothelial Cells; Epoprostenol; Heart Failure; Humans; Hypertension; Mitochondrial Proton-Translocating ATPases; NF-kappa B; Nitric Oxide; Oxidative Phosphorylation Coupling Factors; p38 Mitogen-Activated Protein Kinases; Protein Kinase C; Signal Transduction; Sodium Chloride, Dietary

The concept of mild chronic vascular inflammation as part of the pathophysiology of cardiovascular disease, most importantly hypertension and atherosclerosis, has been well accepted. Indeed there are links between vascular inflammation, endothelial dysfunction and oxidative stress. However, there are still gaps in our understanding regarding this matter that might be the cause behind disappointing results of antioxidant therapy for cardiovascular risk factors in large-scale long-term randomised controlled trials. Apart from the limitations of our knowledge, limitations in methodology and assessment of the body's endogenous and exogenous oxidant-antioxidant status are a serious handicap. The pleiotropic effects of antioxidant and anti-inflammation that are shown by some well-established antihypertensive agents and statins partly support the idea of using antioxidants in vascular diseases as still relevant. This review aims to provide an overview of the links between oxidative stress, vascular inflammation, endothelial dysfunction and cardiovascular risk factors, importantly focusing on blood pressure regulation and atherosclerosis. In view of the potential benefits of antioxidants, this review will also examine the proposed role of vitamin C, vitamin E and polyphenols in cardiovascular diseases as well as the success or failure of antioxidant therapy for cardiovascular diseases in clinical trials.

Topics: Animals; Antihypertensive Agents; Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Endothelium, Vascular; Humans; Hypertension; Inflammation; Oxidative Stress; Reactive Oxygen Species; Risk Factors; Vitamin E

In observational studies, increased vitamin C intake, vitamin C supplementation, and higher blood concentrations of vitamin C are associated with lower blood pressure (BP). However, evidence for blood pressure-lowering effects of vitamin C in clinical trials is inconsistent.. The objective was to conduct a systematic review and meta-analysis of clinical trials that examined the effects of vitamin C supplementation on BP.. We searched Medline, EMBASE, and Central databases from 1966 to 2011. Prespecified inclusion criteria were as follows: 1) use of a randomized controlled trial design; 2) trial reported effects on systolic BP (SBP) or diastolic BP (DBP) or both; 3) trial used oral vitamin C and concurrent control groups; and 4) trial had a minimum duration of 2 wk. BP effects were pooled by random-effects models, with trials weighted by inverse variance.. Twenty-nine trials met eligibility criteria for the primary analysis. The median dose was 500 mg/d, the median duration was 8 wk, and trial sizes ranged from 10 to 120 participants. The pooled changes in SBP and DBP were -3.84 mm Hg (95% CI: -5.29, -2.38 mm Hg; P < 0.01) and -1.48 mm Hg (95% CI: -2.86, -0.10 mm Hg; P = 0.04), respectively. In trials in hypertensive participants, corresponding reductions in SBP and DBP were -4.85 mm Hg (P < 0.01) and -1.67 mm Hg (P = 0.17). After the inclusion of 9 trials with imputed BP effects, BP effects were attenuated but remained significant.. In short-term trials, vitamin C supplementation reduced SBP and DBP. Long-term trials on the effects of vitamin C supplementation on BP and clinical events are needed.

Topics: Ascorbic Acid; Blood Pressure; Dietary Supplements; Humans; Hypertension; Randomized Controlled Trials as Topic; Vitamins

Dietary supplements (DSs) are used extensively in the general population and many are promoted for the natural treatment and management of hypertension. Patients with hypertension often choose to use these products either in addition to or instead of pharmacologic antihypertensive agents. Because of the frequent use of DS, both consumers and health care providers should be aware of the considerable issues surrounding these products and factors influencing both efficacy and safety. In this review of the many DSs promoted for the management of hypertension, 4 products with evidence of possible benefits (coenzyme Q10, fish oil, garlic, vitamin C) and 4 that were consistently associated with increasing blood pressure were found (ephedra, Siberian ginseng, bitter orange, licorice). The goals and objectives of this review are to discuss the regulation of DS, evaluate the efficacy of particular DS in the treatment of hypertension, and highlight DS that may potentially increase blood pressure.

Topics: Ascorbic Acid; Citrus; Dietary Supplements; Eleutherococcus; Ephedra; Fish Oils; Garlic; Glycyrrhiza; Humans; Hypertension; Ubiquinone; United States

The purpose of this review is to highlight recent publications examining nitric oxide production in health and disease and its association with clinical nutrition and alterations in metabolism.. The role of the cofactor tetrahydrobiopterin in nitric oxide production and its relation with arginine availability is indicated as an important explanation for the arginine paradox. This offers potential for nitric oxide regulation by dietary factors such as arginine or its precursors and vitamin C. Because diets with a high saturated fat content induce high plasma fatty acid levels, endothelial nitric oxide production is often impaired due to a reduction in nitric oxide synthase 3 phosphorylation. Increasing the arginine availability by arginine therapy or arginase inhibition was, therefore, proposed as a potential therapy to treat hypertension. Recent studies in septic patients and transgenic mice models found that inadequate de-novo arginine production from citrulline reduces nitric oxide production. Citrulline supplementation may, therefore, be a novel therapeutic approach in conditions of arginine deficiency.. Both lack and excess of nitric oxide production in diseases can have various important implications in which dietary factors can play a modulating role. Future research is needed to expand our understanding of the regulation and adequate measurement of nitric oxide production at the organ level and by the different nitric oxide synthase isoforms, also in relation to clinical nutrition.

Topics: Animals; Arginase; Arginine; Ascorbic Acid; Biopterins; Citrulline; Diet; Dietary Fats; Endothelium; Humans; Hypertension; Mice; Nitric Oxide; Nitric Oxide Synthase Type III; Sepsis

Despite the apparent consensus on the existence of endothelial dysfunction in conduit and resistance arteries of spontaneously hypertensive rats (SHR), a commonly employed experimental model of hypertension, there are a number of reports showing that endothelium-dependent vasodilatory responses are similar, or even increased, in SHR compared with their normotensive counterparts. The present paper aims to discuss the rationale for these apparent discrepancies, including the effect of age, type of artery and methodological aspects. Data from the literature indicate that the age of the animal is a contributing factor and that endothelial dysfunction is likely to be a consequence of hypertension. In addition, the use of antioxidant additives, such as ascorbic acid or ethylene diaminetetraacetic acid, and differences in the level of initial arterial stretch, might also be of importance because they may modify the oxidative status of the artery and the levels of vasoactive factors released by the endothelium.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Disease Models, Animal; Edetic Acid; Endothelium, Vascular; Hypertension; Nitric Oxide; Oxidative Stress; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Species Specificity

Growing evidence indicates that insulin resistance and oxidative stress are involved in the pathogenesis of essential hypertension. In insulin-resistant states, like obesity and type 2 diabetes, altered glucose metabolism may lead to increased formation of methylglyoxal and other ketoaldehydes. Animal studies have shown that increased levels of endogenous aldehydes may lead to hypertension and oxidative stress. In animal models, the administration of vitamin C, vitamin B6 or alpha-lipoic acid reduced tissue levels of aldehydes, prevented oxidative stress, and lowered blood pressure. The purpose of this review article is to critically evaluate the available evidence for the role of dietary supplements in hypertension treatment.

Topics: Aldehydes; Animals; Ascorbic Acid; Dietary Supplements; Evidence-Based Medicine; Glucose Intolerance; Humans; Hypertension; Insulin Resistance; Thioctic Acid; Vitamin B 6

The clinical use of antioxidants has gained considerable interest during the last decade. It was suggested from epidemiological studies that diets high in fruits and vegetables might help decrease the risk of cardiovascular disease. Therefore, supplements of vitamins C and E were applied through protocols aimed to prevent diseases such as atherosclerosis, preeclampsia or hypertension, thought to be mediated by oxidative stress. Despite the biological properties of these vitamins could account for an effective protection, as shown by several clinical and experimental studies, their efficacy remains controversial in the light of some recent clinical trials and meta-analyses. However, the methodology of these studies, criteria for selection of patients, the uncertain extent of progression of the disease when initiating supplementation, the lack of mechanistic studies containing basic scientific aspects, such as the bioavailability, pharmacokinetic properties, and the nature of the antioxidant sources of vitamins, could account for the inconsistency of the various clinical trials and meta-analyses assessing the efficacy of these vitamins to prevent human diseases. This review presents a survey of the clinical use of antioxidant vitamins E and C, proposing study models based on the biological effects of these compounds likely to counteract the pathophysiological mechanisms able to explain the structural and functional organ damage.

Topics: Antioxidants; Ascorbic Acid; Atherosclerosis; Female; Humans; Hypertension; Models, Biological; Oxidative Stress; Pre-Eclampsia; Pregnancy; Vitamin E; Vitamins

1. In the present review, we addressed studies in humans and rats to determine the role that oxidative stress may play in mediating cardiovascular outcomes. 2. Biochemical evaluation of oxidative stress in both humans and spontaneously hypertensive rats gives equivocal results as to the relative levels in males versus females. Clinical trials with anti-oxidants in humans have not shown consistent results in protecting against detrimental cardiovascular outcomes. In spontaneously hypertensive rats (SHR), blockade studies using tempol or apocynin reduce renal oxidative stress and blood pressure in male SHR, but not in female rats. In addition, increasing oxidative stress with molsidomine increases blood pressure in male, but not female, SHR. Treatment with vitamins E and C reduces blood pressure in young male, but not aged, animals. Furthermore tempol is unable to reduce blood pressure in young male SHR in the absence of a functional nitric oxide system. 3. Neither human nor animal studies are consistent in terms of whether oxidative stress levels are higher in males or females. Furthermore, anti-oxidant therapy in humans often does not ameliorate, or even attenuate, the negative cardiovascular consequences of increased oxidative stress. Our studies in SHR shed light on why these outcomes occur.

Topics: Acetophenones; Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Cardiovascular Diseases; Catalase; Cyclic N-Oxides; Enzyme Inhibitors; Female; Glutathione Peroxidase; Humans; Hypertension; Kidney; Male; Molsidomine; NADPH Oxidases; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Oxidative Stress; Rats; Rats, Inbred SHR; Sex Factors; Spin Labels; Superoxide Dismutase; Vitamin E

Diabetes represents a serious risk factor for the development of cardiovascular problems such as coronary heart disease, peripheral arterial disease, hypertension, stroke, cardiomyopathy, nephropathy and retinopathy. Identifying the pathogenesis of this increased risk provides a basis for secondary intervention to reduce morbidity and mortality in diabetic patients. Hyperglycemia and protein glycation, increased inflammation, a prothrombotic state and endothelial dysfunction have all been implicated as possible mechanisms for such complications. A linking element between many of these phenomena could possibly be, among other factors, increased production of reactive oxygen species. Vascular endothelial cells have several physiological actions that are essential for the normal function of the cardiovascular system. These include the production of nitric oxide (NO), which regulates vasodilatation, anticoagulation, leukocyte adhesion, smooth muscle proliferation and the antioxidative capacity of endothelial cells. However, under conditions of hyperglycemia, excessive amounts of superoxide radicals are produced inside vascular cells and this can interfere with NO production leading to the possible complications. This article aims at reviewing the links between reactive oxygen species, diabetes and vascular disease and whether or not antioxidants can alter the course of vascular complications in diabetic patients and animal models. A possible beneficial effect of antioxidants might present a new addition to the range of secondary preventive measures used in diabetic patients.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Complications; Dyslipidemias; Endothelium, Vascular; Glucose; Humans; Hyperglycemia; Hypertension; Insulin Resistance; Nitric Oxide; Oxidative Stress; Reactive Oxygen Species; Risk Factors; Vitamin E

This review gives a brief overview of the main types of dementia and summarizes current thinking on the relationship between nutritional-related factors and disorders, and dementia. Dementia is a multi-factor pathological condition, and nutrition is one factor that may play a role on its onset and progression. An optimal intake of nutrients doesn't protect people from dementia. However, studies in this area show that inadequate dietary habits, which are of particular concern in elderly populations, may increase the risk of developing a number of age-related diseases, including disorders of impaired cognitive function. They show that a deficiency in essential nutrients, such as certain B complex vitamins, can result in hyperhomocysteinemia, a well-known risk factor for atherosclerosis and recently associated with cognitive impairment in old age. A deficiency of antioxidants such as vitamins C and E, and beta-carotene, as well as nutrition-related disorders like hypercholesterolemia, hypertension, and diabetes, may also have some role in cognitive impairment. These factors can be present for a long time before cognitive impairment becomes evident, therefore they could be potentially detected and corrected in a timely manner.

Topics: Alzheimer Disease; Antioxidants; Ascorbic Acid; Dementia; Diabetes Mellitus; Diet; Humans; Hyperhomocysteinemia; Hyperlipidemias; Hypertension; Nutrition Disorders; Nutritional Physiological Phenomena; Oxidative Stress; Risk Factors; Vitamin A; Vitamin B Complex; Vitamin E

The goal of this review is to evaluate the efficacy of commonly available dietary supplements in the treatment of hypertension, using the average blood pressure reduction achieved with the implementation of lifestyle modifications as a standard. For this reason, the authors focus on the antihypertensive potential of these agents rather than pharmacology, pharmacokinetics, adverse effects, or supplement-drug interactions. For the purpose of this review, dietary supplements are defined as exhibiting some evidence of benefit if a systolic blood pressure reduction of 9.0 mm Hg or greater and/or a diastolic blood pressure reduction of 5.0 mm Hg or greater has been observed in previously published, peer-reviewed trials. These defining limits are based on the average blood pressure reduction associated with the implementation of certain lifestyle modifications. Agents with some evidence of benefit include coenzyme Q10, fish oil, garlic, vitamin C, and L-arginine.

Topics: Antihypertensive Agents; Arginine; Ascorbic Acid; Coenzymes; Complementary Therapies; Dietary Supplements; Fish Oils; Garlic; Humans; Hypertension; Treatment Outcome; Ubiquinone

Oxidative stress is involved in the pathogenesis of atherosclerosis, while a variety of antioxidants has been used in clinical studies, during the past few years, for the prevention and treatment of atherosclerosis. In small clinical studies it was found that both vitamins C and E may improve endothelial function in patients with risk factors for atherosclerosis such as diabetes mellitus, smoking, hypertension, or hypercholesterolemia. However, the initial, hopeful reports regarding the beneficial role of antioxidant vitamins against atherosclerosis, derived from purely observational studies, were followed by the negative results of almost all large randomized trials. Therefore, treatment with antioxidant vitamins C and E should not be recommended for the prevention or treatment of coronary atherosclerosis. New antioxidant strategies are needed to clarify the exact role of antioxidant treatment in coronary atherosclerosis.

Topics: Adult; Aged; Aged, 80 and over; Animals; Antioxidants; Arteriosclerosis; Ascorbic Acid; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Coronary Artery Disease; Diabetes Complications; Diet; Endothelium, Vascular; Female; Follow-Up Studies; Free Radicals; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Oxidative Stress; Prospective Studies; Randomized Controlled Trials as Topic; Risk; Risk Factors; Smoking; Time Factors; Vitamin E

Oxidation is a biochemical process of loss of electrons associated with another of reception called reduction. This process is capital for life, because it takes part in the production of cellular energy. Oxidative stress appears when oxidation is excessive. This reality is complex in all biological levels, and cannot be measured or defined by a single parameter. A great number of diseases have been related to oxidative stress and generation of free radicals. For this reason, antioxidant therapies and diets (such as mediterranean diet) rich or enriched with antioxidants seem to prevent or at least to attenuate the organic deterioration originated by an excessive oxidative stress.

Topics: Acute Kidney Injury; Aged; Aging; Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Cataract; Diabetes Mellitus; Diet; Humans; Hypertension; Liver Diseases; Neoplasms; Oxidation-Reduction; Oxidative Stress; Primary Prevention; Risk Factors; Selenium; Vitamin E

Topics: Ascorbic Acid; Blood Pressure; Humans; Hypertension; Vitamin D; Vitamin E

Topics: Animals; Antioxidants; Ascorbic Acid; Chronic Disease; Endothelium, Vascular; Free Radicals; Heart Failure; Humans; Hypertension; Nitric Oxide; Renin-Angiotensin System

Evidence for a 'third factor' in the regulation of urinary sodium excretion has directed a search for a natriuretic agent which functions by inhibition of Na,K-ATPase. Such an agent may also be involved in the genesis of hypertension and provide an important pathophysiological link between increased sodium intake, reduced renal sodium excretory capacity and hypertension. Numerous lines of evidence have been developed, all supporting the possibility that third factor sodium pump inhibition may take place through the cardiac glycoside-binding site of the sodium pump. Inhibition of the sodium pump may contribute to renal mechanisms of sodium balance. Generalization of this inhibition to vascular tissue and to the neural tissue regulating vascular contraction may elevate blood pressure (and increase natriuresis) by increasing contraction. In spite of 30 years of effort, no convincing substance has been successfully identified as both a cardiac glycoside-like inhibitor of the sodium pump and an endogenous substance. However, recent work has led to the emergence and investigation of a number of interesting candidates. This review will survey the historical background of endogenous sodium pump inhibitors, examine some of the problems and requirements which must be overcome in their identification, analyze evidence obtained recently concerning a number of candidate compounds and identify problems which remain to be addressed in this field.

Topics: Animals; Ascorbic Acid; Enzyme Inhibitors; Humans; Hypertension; Ouabain; Sodium; Sodium-Potassium-Exchanging ATPase

Topics: Alcohol Drinking; Animals; Ascorbic Acid; Cerebrovascular Disorders; Colonic Neoplasms; Diet; Esophageal Neoplasms; Female; Fishes; Food Preservation; Food Preservatives; Humans; Hypertension; Male; Nitrites; Risk; Smoking; Stomach Neoplasms

Topics: Adrenal Cortex Hormones; Adrenal Glands; Adrenocorticotropic Hormone; Aldosterone; Animals; Ascorbic Acid; Cholesterol; Contraceptives, Oral; Glucocorticoids; Glucose; Hydroxycorticosteroids; Hypertension; In Vitro Techniques; Mitochondria; Mixed Function Oxygenases; Pituitary Gland; Potassium; Rats; Sodium

Topics: Adult; Aged; Animals; Arteriosclerosis; Ascorbic Acid; Catecholamines; Diet Therapy; Dietary Fats; Fats, Unsaturated; Female; Humans; Hypercholesterolemia; Hyperlipidemias; Hypertension; Injections, Intra-Arterial; Intermittent Claudication; Male; Mice; Middle Aged; Myocardial Infarction; Nicotine; Obesity; Procaine; Rabbits; Radiography; Smoking; Sympathectomy; Thiamine; Thromboangiitis Obliterans; Tolazoline; Vasodilator Agents

The objective of this study was to determine the association between sociodemographic factors and intakes of 4 nutrients and associations between intakes and markers of kidney disease to identify opportunities to improve outcomes among clinically high-risk African Americans.. We conducted a cross-sectional study of baseline data from the Achieving Blood Pressure Control Together study, a randomized controlled trial of 159 African Americans (117 females) with uncontrolled hypertension in Baltimore MD. To determine the association between sociodemographic factors and nutrient intakes, we constructed linear and logistic regression models. Using logistic regression, we determined the association between below-median nutrient intakes and kidney disease. Our outcomes of interest were daily intakes of vitamin C, magnesium, dietary fiber, and potassium as estimated by the Block Fruit-Vegetable-Fiber Screener and kidney disease defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2 or urinary albumin-to-creatinine ratio >=30 mg/g.. Baseline data from the Achieving Blood Pressure Control Together study, a randomized controlled trial of 159 African Americans (117 females) with uncontrolled hypertension, were obtained.. To determine the association between sociodemographic factors and nutrient intakes, we constructed linear and logistic regression models. Using logistic regression, we determined the association between below-median nutrient intakes and kidney disease.. Overall, compared to Institute of Medicine recommendations, participants had lower intakes of magnesium, fiber, and potassium but higher vitamin C intakes. For females, sociodemographic factors that significantly associated with lower intake of the 4 nutrients were older age, obesity, lower health numeracy, and lesser educational attainment. For males, none of the sociodemographic factors were significantly associated with nutrient intakes. Below-median intake was significantly associated with albumin-to-creatinine ratio ≥30 (adjusted odds ratio [95% confidence interval]: 3.4 [1.5, 7.8] for vitamin C; 3.6 [1.6, 8.4] for magnesium; 2.9 [1.3, 6.5] for fiber; 3.6 [1.6, 8.4] for potassium), but not with estimated glomerular filtration rate <60.. African Americans with uncontrolled hypertension may have low intakes of important nutrients, which could increase their risk of chronic kidney disease. Tailored dietary interventions for African Americans at high risk for chronic kidney disease may be warranted.

Topics: Aged; Ascorbic Acid; Baltimore; Black or African American; Blood Pressure; Cross-Sectional Studies; Diet; Dietary Fiber; Energy Intake; Female; Humans; Hypertension; Kidney Diseases; Logistic Models; Magnesium; Male; Middle Aged; Nutritional Status; Potassium, Dietary; Socioeconomic Factors; Surveys and Questionnaires; Urban Population

Obesity is well associated as being an interfering factor in metabolic diseases such as hypertension and diabetes by increasing the secretion of proinflammatory markers from adipose tissue. Having healthy effects, vitamin C could work as an anti-inflammatory agent through its antioxidant capacity.. FPSK_Mac [13]04.. The aim of the study reported here was to identify the effect of vitamin C on reducing the levels of inflammatory markers in hypertensive and/or diabetic obese adults.. Sixty-four obese patients, who were hypertensive and/or diabetic and had high levels of inflammatory markers, from primary health care centers in Gaza City, Palestine, were enrolled into one of two groups in an open-label, parallel, randomized controlled trial. A total of 33 patients were randomized into a control group and 31 patients were randomized into an experimental group. The experimental group was treated with 500 mg vitamin C twice a day.. In the experimental group, vitamin C significantly reduced the levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), fasting blood glucose (FBG), and triglyceride (TG) after 8 weeks of treatment (overall: P<0.001); no changes appeared in total cholesterol (TC). In the control group, there were significant reductions in FBG and TG (P=0.001 and P=0.026, respectively), and no changes in hs-CRP, IL-6, or TC. On comparing the changes in the experimental group with those in the control group at the endpoint, vitamin C was found to have achieved clinical significance in treating effectiveness for reducing hs-CRP, IL-6, and FBG levels (P=0.01, P=0.001, and P<0.001, respectively), but no significant changes in TC or TG were found.. Vitamin C (500 mg twice daily) has potential effects in alleviating inflammatory status by reducing hs-CRP, IL-6, and FBG in hypertensive and/or diabetic obese patients.

Topics: Administration, Oral; Adult; Anti-Infective Agents; Ascorbic Acid; Biomarkers; Blood Glucose; C-Reactive Protein; Cholesterol; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Humans; Hypertension; Inflammation; Inflammation Mediators; Interleukin-6; Male; Middle Aged; Obesity; Time Factors; Treatment Outcome; Triglycerides; Young Adult

Abstract Oxidative stress (OS) plays a key role in the pathophysiology of essential hypertension and is associated with changes in the cell membrane fatty acid composition and fluidity. As (Na,K)-ATPase is modulated by the surrounding lipid microenvironment, lipid peroxidation could alter the interactions of this enzyme with the membrane components. Thus, modifications in the membrane fatty acid profile will translate into effects on (Na,K)-ATPase activity. Accordingly, a decrease in this enzyme activity has been reported in hypertensive patients. The aim of this study was to evaluate the relationship between membrane fluidity and fatty acid composition and (Na,K)-ATPase activity in erythrocytes of essential hypertensive patients supplemented with antioxidant vitamins C and E. A double-blind, randomized, placebo-controlled study was conducted in 120 men with essential hypertension assigned to receive vitamin C (1 g/day) +E (400 IU/day) or placebo for 8 weeks. Measurements included OS related parameters: GSH/GSSG ratio, F2-isoprostanes and antioxidant capacity of plasma, (Na,K)-ATPase activity and erythrocytes membrane fatty acid composition (PUFA, polyunsaturated fatty acids; SAFA, saturated fatty acids). Associations were assessed by Pearson correlation and the differences by Student t-test (p<0.05). Supplemented hypertensive patients showed higher activity of (Na,K)-ATPase and proportion of PUFA, and lower blood pressure, OS markers and proportion of SAFA, versus placebo. The activity of (Na,K)-ATPase correlated negatively with the proportion of SAFA, but positively with that of PUFA in both groups. Supplementation with vitamins C+E resulted in decreased OS and increased fluidity and PUFA proportion in the membrane, both of which positively modulate (Na,K)-ATPase activity, accounting for the blood pressure reduction.

Topics: Adult; Antioxidants; Ascorbic Acid; Blood Pressure; Double-Blind Method; Erythrocyte Membrane; Erythrocytes; Essential Hypertension; Fatty Acids; Fatty Acids, Unsaturated; Humans; Hypertension; Male; Membrane Fluidity; Membrane Lipids; Middle Aged; Oxidative Stress; Sodium-Potassium-Exchanging ATPase; Vitamin E; Vitamins

High blood pressure (BP) variability, which may be an important determinant of hypertensive end-organ damage, is emerging as an important predictor of cardiovascular health. Dietary antioxidants can influence BP, but their effects on variability are yet to be investigated. The aim of the present study was to assess the effects of vitamin E, vitamin C and polyphenols on the rate of daytime and night-time ambulatory BP variation. To assess these effects, two randomised, double-blind, placebo-controlled trials were performed. In the first trial (vitamin E), fifty-eight individuals with type 2 diabetes were given 500 mg/d of RRR-α-tocopherol, 500 mg/d of mixed tocopherols or placebo for 6 weeks. In the second trial (vitamin C-polyphenols), sixty-nine treated hypertensive individuals were given 500 mg/d of vitamin C, 1000 mg/d of grape-seed polyphenols, both vitamin C and polyphenols, or neither (placebo) for 6 weeks. At baseline and at the end of the 6-week intervention, 24 h ambulatory BP and rate of measurement-to-measurement BP variation were assessed. Compared with placebo, treatment with α-tocopherol, mixed tocopherols, vitamin C and polyphenols did not significantly alter the rate of daytime or night-time systolic BP, diastolic BP or pulse pressure variation (P>0·05). Treatment with the vitamin C and polyphenol combination resulted in higher BP variation: the rate of night-time systolic BP variation (P= 0·022) and pulse pressure variation (P= 0·0036) were higher and the rate of daytime systolic BP variation was higher (P= 0·056). Vitamin E, vitamin C or grape-seed polyphenols did not significantly alter the rate of BP variation. However, the increase in the rate of BP variation suggests that the combination of high doses of vitamin C and polyphenols could be detrimental to treated hypertensive individuals.

Topics: Aged; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Blood Pressure; Diet; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Placebos; Polyphenols; Seeds; Tocopherols; Vitamin E; Vitis

Hypertension occurs in 6 to 10 percent of pregnancies. It remains one of the most common disorders in pregnancy and the leading causes of maternal and fetal morbidity The changes in blood vessel endothelium have impact on the pathogenesis of hypertension and preeclampsia.. The aim of this study was to establish endothelin- 1 and lipids peroxides content in blood during hypertension and the influence of vitamin C and E supplementation on the concentration of both parameters.. Two study groups (pregnancy complicated with hypertension, pregnancy complicated with hypertension treated with vitamins C and E) and a control group with uncomplicated pregnancies were distinguished. Blood samples from maternal peripheral venous circulation were collected and ET-1 and lipids peroxides levels were determined from the blood samples.. Concentration of endothelin-1 in the group with hypertension and with vitamin supplementation was INCREASED (66.18 +/- 26.66 pg/ml) in comparison with normal pregnant (36.50 +/- 13.25) and hypertension group (41.02 +/- 15.98). The difference was significant. Lipid peroxides concentrations were significantly higher in the group with hypertension (1.18 +/- 0.69) in comparison with both groups - controls (0.73 +/- 0.35) and the group with hypertension and vitamin supplementation (0.77 +/- 0.42).. No significant differences in the endothelin- 1 level between healthy pregnant and pregnant women with hypertension were found. Vitamin supplementation decreases the concentrations of lipid peroxides.

Topics: Administration, Oral; Ascorbic Acid; Biomarkers; Drug Administration Schedule; Endothelin-1; Female; Humans; Hypertension; Hypertension, Pregnancy-Induced; Lipid Peroxides; Pregnancy; Vitamin E

The effects of the Dietary Approaches to Stop Hypertension (DASH) eating plan on childhood metabolic syndrome (MetS) and insulin resistance remain to be determined. The present study aimed to assess the effects of recommendations to follow the DASH diet v. usual dietary advice (UDA) on the MetS and its features in adolescents. In this randomised cross-over clinical trial, sixty post-pubescent adolescent girls with the MetS were randomly assigned to receive either the recommendations to follow the DASH diet or UDA for 6 weeks. After a 4-week washout period, the participants were crossed over to the alternate arm. The DASH group was recommended to consume a diet rich in fruits, vegetables and low-fat dairy products and low in saturated fats, total fats and cholesterol. UDA consisted of general oral advice and written information about healthy food choices based on healthy MyPlate. Compliance was assessed through the quantification of plasma vitamin C levels. In both the groups, fasting venous blood samples were obtained at baseline and at the end of each phase of the intervention. The mean age and weight of the participants were 14.2 (SD 1.7) years and 69 (SD 14.5) kg, respectively. Their mean BMI and waist circumference were 27.3 kg/m2 and 85.6 cm, respectively. Serum vitamin C levels tended to be higher in the DASH phase than in the UDA phase (860 (SE 104) v. 663 (SE 76) ng/l, respectively, P= 0.06). Changes in weight, waist circumference and BMI were not significantly different between the two intervention phases. Although changes in systolic blood pressure were not statistically significant between the two groups (P= 0.13), recommendations to follow the DASH diet prevented the increase in diastolic blood pressure compared with UDA (P= 0.01). We found a significant within-group decrease in serum insulin levels (101.4 (SE 6.2) v. 90.0 (SE 5.5) pmol/l, respectively, P= 0.04) and a non-significant reduction in the homeostasis model assessment for insulin resistance score (P= 0.12) in the DASH group. Compared with the UDA group, the DASH group experienced a significant reduction in the prevalence of the MetS and high blood pressure. Recommendations to follow the DASH eating pattern for 6 weeks among adolescent girls with the MetS led to reduced prevalence of high blood pressure and the MetS and improved diet quality compared with UDA. This type of healthy diet can be considered as a treatment modality for the MetS and its components in children.

Topics: Adolescent; Ascorbic Acid; Blood Pressure; Body Mass Index; Child; Cross-Over Studies; Female; Humans; Hypertension; Insulin; Insulin Resistance; Metabolic Syndrome; Patient Compliance; Prevalence; Waist Circumference

Oxidative stress could play a role in the development of preeclampsia. There is some evidence to suggest that vitamin C and E supplements can reduce the risk of the disorder. We hypothesized its beneficial role in a group of pregnant women with essential hypertension.. In this randomized controlled trial, we enrolled 50 pregnant women with essential hypertension. We assigned the women 1000 mg vitamin C and 400 IU natural vitamin E (RRR α tocopherol; n = 25), daily from the second trimester of pregnancy until delivery or no supplementation (n = 25). Our primary endpoint was development of superimposed preeclampsia, and main secondary endpoints were aggravation of hypertension, need for admission, need to increase antihypertensive drugs, and small size for gestational age (

Topics: Adult; Antioxidants; Ascorbic Acid; Female; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Risk Factors; Treatment Outcome; Vitamin E

Endothelin-1 (ET-1) is a key regulator of arterial blood pressure in humans, and homocysteinemia is associated with increased oxidative stress. It is still unclear whether homocysteine-induced oxidative stress is implicated in the regulation of ET-1 expression. We examined the impact of acute homocysteinemia on endothelial function in hypertensive patients and healthy individuals, and the potential role of ET-1.. In this double-blind, placebo-controlled study, 39 hypertensive and 49 healthy individuals were randomized to receive high-dose vitamins (2 g vitamin C and 800IU vitamin E) or placebo followed by methionine loading 100 mg/kg body weight. Endothelium-dependent dilation (EDD) and endothelium-independent dilation (EID) of the brachial artery were evaluated by plethysmography, at baseline and 4 h postloading (4 h PML). ET-1 was measured by ELISA, whereas total lipid hydroperoxides (per-ox) levels were measured by a commercially available photometric technique.. Acute, methionine-induced homocysteinemia decreased EDD in all study groups (P < 0.001 for all), whereas vitamins pretreatment failed to prevent this effect, despite the vitamins-induced reduction of peroxidation in the hypertensives group (P < 0.05). On the contrary, methionine loading significantly increased plasma ET-1 levels only in hypertensives (P < 0.05), an effect which was not prevented by antioxidant vitamins (P < 0.05). EID remained unchanged after methionine loading, in all study groups (P = NS for all groups).. Experimental homocysteinemia rapidly blunts endothelial function in both hypertensive individuals and healthy individuals. The rapid elevation of ET-1 levels observed only in hypertensives, suggests that ET-1 may be the key mediator of homocysteine-induced endothelial dysfunction, independently of oxidative stress.

Topics: Adult; Ascorbic Acid; Double-Blind Method; Endothelin-1; Endothelium, Vascular; Female; Homocysteine; Humans; Hyperhomocysteinemia; Hypertension; Male; Methionine; Oxidative Stress; Signal Transduction; Vasodilation; Vitamin E

In a placebo-controlled double-blinded study, the effect of 8 weeks of grape juice was compared to the effect of isocaloric placebo juice. Volunteers with a systolic blood pressure > 130 mmHg and diastolic blood pressure > 90 mmHg were recruited. A total of 40 healthy subjects were randomized to receive isocaloric juices for 8 weeks. Twenty-one subjects were instructed to consume 5.5 mL/kg daily of grape juice (GJ), and 19 subjects consumed placebo juice (PJ). Plasma antioxidant vitamin C, total radical trapping antioxidant capacity, blood pressure, and lymphocyte DNA damage were assessed pre- and postsupplementation. Plasma total radical-trapping antioxidant potential showed an increase at the level of 1.31 +/- 0.01 (postsupplementation) versus 1.33 +/- 0.01 (presupplementation) (P < 0.1). Grape juice consumption resulted in a 26% decrease in lymphocyte DNA (both hydrogen peroxide treated or spontaneous) in the grape juice group, while no difference was found in the PJ group. Consuming moderate amounts of daily grape juice may favorably affect antioxidant defense systems and lymphocyte DNA damage in hypertensive individuals.

Topics: Adult; Antioxidants; Ascorbic Acid; Beverages; Blood Pressure; Catalase; DNA Damage; Double-Blind Method; Humans; Hypertension; Lipids; Lymphocytes; Middle Aged; Time Factors; Treatment Outcome; Vitis

Oxidative stress has been associated with mechanisms of EH (essential hypertension). The aim of the present study was to test the hypothesis that the antioxidant properties of vitamins C and E are associated with a decrease in BP (blood pressure) in patients with EH. A randomized double-blind placebo-controlled clinical trial was conducted in 110 men with grade 1 EH (35-60 years of age without obesity, dyslipidaemia and diabetes mellitus, non-smokers, not undergoing vigorous physical exercise, without the use of any medication and/or high consumption of fruit and vegetables). Participants were randomly assigned to receive either vitamins C+E [vitamin C (1 g/day) plus vitamin E (400 international units/day)] or placebo for 8 weeks. Measurements included 24 h ambulatory BP and blood analysis of oxidative-stress-related parameters in erythrocytes (GSH/GSSH ratio, antioxidant enzymes and malondialdehyde) and plasma [FRAP (ferric reducing ability of plasma)], and levels of 8-isoprostane, vitamins C and E were measured at baseline and after treatment. Following administration of vitamins C+E, patients with EH had significantly lower systolic BP, diastolic BP and mean arterial BP and higher erythrocyte and serum antioxidant capacity compared with either placebo-treated patients with EH or the patients with EH at baseline prior to treatment. BP correlated positively with plasma 8-isoprostane levels and negatively with plasma FRAP levels in the vitamins C+E- and placebo-treated groups. In conclusion, the present study supports the view that oxidative stress is involved in the pathogenesis of EH, and that enhancement of antioxidant status by supplementation with vitamins C and E in patients with EH is associated with lower BP. This suggests intervention with antioxidants as an adjunct therapy for hypertension.

Topics: Adult; Analysis of Variance; Antioxidants; Ascorbic Acid; Blood Pressure Determination; Dinoprost; Double-Blind Method; Erythrocytes; Humans; Hypertension; Iron; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Treatment Outcome; Vitamin E; Vitamins

Prospective contemporaneous data on the outcome of pregnancies in women with chronic hypertension are sparse. Indices of maternal and perinatal morbidity and mortality were determined in 822 women with chronic hypertension with data prospectively collected and rigorously validated. The incidence of superimposed preeclampsia was 22% (n=180) with early-onset preeclampsia (

Topics: Adult; Antioxidants; Ascorbic Acid; Chronic Disease; Female; Humans; Hypertension; Morbidity; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Prevalence; Prospective Studies; Risk Factors; Smoking; Vitamin E

Essential hypertension is characterized by endothelial dysfunction, arterial stiffness, and increased oxidative stress. We evaluated the effect of short-term combined treatment with the antioxidants vitamins C and E on endothelial function, arterial stiffness, and oxidative stress in untreated essential hypertensive patients.. A randomized, double-blind, placebo-controlled, crossover study design was used to assign 30 male essential hypertensive patients to either vitamin C (1 g) and vitamin E (400 IU) or placebo for 8 weeks. Endothelium-dependent response was assessed as flow-mediated dilation (FMD) of the brachial artery. Arterial stiffness was assessed as central pulse wave velocity (PWV) and augmentation index (AIx). Plasma markers of oxidative stress and antioxidant status were measured.. After vitamin supplementation, FMD was significantly improved. Central PWV was significantly reduced, while AIx tended to decrease. Plasma vitamin levels and antioxidant capacity increased significantly. Levels of oxidative stress decreased. Changes in central PWV were related to changes in levels of oxidative stress.. Combined treatment with vitamins C and E has beneficial effects on endothelium-dependent vasodilation and arterial stiffness in untreated, essential hypertensive patients. This effect is associated with changes in plasma markers of oxidative stress.

Topics: Adult; Antioxidants; Ascorbic Acid; Atherosclerosis; Blood Pressure; Brachial Artery; Cross-Over Studies; Dietary Supplements; Double-Blind Method; Drug Therapy, Combination; Endothelium, Vascular; Humans; Hypertension; Male; Middle Aged; Oxidative Stress; Regional Blood Flow; Vasodilation; Vitamin E

The combined effect of dried Eclipta alba leaf powder (3 g/day) in encapsulated form on blood pressure, diuresis, and lipid profile of 60 mildly hypertensive male subjects in the age group of 40-55 years was studied. The subjects were divided into two groups, i.e., a control (placebo) and the Eclipta group, and were given six capsules (500 mg each) per day in three equal doses for a period of 60 days. Clinical parameters, viz., blood pressure, urine volume, electrolytes (Na and K) in serum and urine, lipid profile, and plasma lipid peroxides, were analyzed before and after the feeding trials. The findings revealed that the Eclipta-supplemented group showed a marked reduction in mean arterial pressure by 15%, total cholesterol (17%), low-density lipoprotein fraction (24%), triglycerides (14%), very-low-density lipoprotein fraction (14%), and plasma lipid peroxides (18%). Results also revealed a remarkable increase in urine volume (34%), urine sodium (24%), serum vitamin C (17%), and serum tocopherols (23%) of the Eclipta group. In conclusion, it would appear that E. alba is diuretic, hypotensive, and hypocholesterolemic and helps in the alleviating oxidative stress-induced complications in hypertensives.

Topics: Adult; Anticholesteremic Agents; Antihypertensive Agents; Ascorbic Acid; Blood Pressure; Diuresis; Diuretics; Eclipta; Humans; Hypertension; Lipid Peroxides; Lipids; Male; Middle Aged; Natriuresis; Phytotherapy; Placebos; Plant Extracts; Plant Leaves; Tocopherols

Anti-hypertensive agents with antioxidative effects are potentially useful for diabetic patients with hypertension to prevent the onset and progression of their complication. While dihydropyridine-type calcium antagonists are among the frequently used anti-hypertensive drugs, azelnidipine, a novel calcium antagonist, has been reported to have a unique anti-oxidative effect in vitro and in animals. In this study, we measured lipid hydroperoxides in human sample using diphenyl-1-pyrenylphosphine for the first time, and used the value of lipid hydroperoxides as an index of oxidative stress. Then, we compared the antioxidative properties of azelnidipine and amlodipine, a frequently used calcium antagonist in hypertensive diabetic patients. Administration of vitamin C and E for 8 weeks significantly reduced lipid hydroperoxides in erythrocyte membrane in normal subjects. In hypertensive diabetic patients, azelnidipine treatment for 12 weeks induced a more significant fall in erythrocyte lipid hydroperoxide level than amlodipine, though blood pressure during each treatment was comparable. Our data confirm the usefulness of lipid hydroperoxides in erythrocyte membrane as a marker of oxidative stress in vivo, and indicate that azelnidipine has a unique antioxidative property in human.

Topics: Adult; Aged; Amlodipine; Antihypertensive Agents; Ascorbic Acid; Azetidinecarboxylic Acid; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Dihydropyridines; Erythrocytes; Female; Humans; Hypertension; Lipid Peroxides; Male; Middle Aged; Organophosphorus Compounds; Pyrenes; Vitamin E

To study whether antioxidant supplementation will reduce the incidence of preeclampsia among patients at increased risk.. A randomized, placebo-controlled, double-blind clinical trial was conducted at four Brazilian sites. Women between 12 0/7 weeks and 19 6/7 weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomly assigned to daily treatment with both vitamin C (1,000 mg) and vitamin E (400 International Units) or placebo. Analyses were adjusted for clinical site and risk group (prior preeclampsia, chronic hypertension, or both). A sample size of 734 would provide 80% power to detect a 40% reduction in the risk of preeclampsia, assuming a placebo group rate of 21% and alpha=.05. The alpha level for the final analysis, adjusted for interim looks, was 0.0458.. Outcome data for 707 of 739 randomly assigned patients revealed no significant reduction in the rate of preeclampsia (study drug, 13.8% [49 of 355] compared with placebo, 15.6% [55 of 352], adjusted risk ratio 0.87 [95.42% confidence interval 0.61-1.25]). There were no differences in mean gestational age at delivery or rates of perinatal mortality, abruptio placentae, preterm delivery, and small for gestational age or low birth weight infants. Among patients without chronic hypertension, there was a slightly higher rate of severe preeclampsia in the study group (study drug, 6.5% [11 of 170] compared with placebo, 2.4% [4 of 168], exact P=.11, odds ratio 2.78, 95% confidence interval 0.79-12.62).. This trial failed to demonstrate a benefit of antioxidant supplementation in reducing the rate of preeclampsia among patients with chronic hypertension and/or prior preeclampsia.. ClinicalTrials.gov, www.ClinicalTrials.gov, NCT00097110. I.

Topics: Adult; Antioxidants; Ascorbic Acid; Double-Blind Method; Female; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Vitamin E

To assess whether dietary intervention in free-living healthy subjects is effective in improving blood pressure levels.. Open randomised, controlled trial.. Free-living healthy subjects in two rural villages in north-eastern Japan.. Five hundred and fifty healthy volunteers aged 40-69 years.. Tailored dietary education to encourage a decrease in sodium intake and an increase in the intake of vitamin C and carotene, and of fruit and vegetables.. Blood pressure, dietary intake and urinary excretion of sodium, dietary carotene and vitamin C, and fruit and vegetable intake data were collected at 1 year after the start of the intervention.. During the first year, changes differed significantly between the intervention and control groups for dietary (P = 0.002) and urinary excretion (P < 0.001) of sodium and dietary vitamin C and carotene (P = 0.003). Systolic blood pressure decreased from 127.9 to 125.2 mmHg (2.7 mmHg decrease; 95% confidence interval, -4.6 to -0.8) in the intervention group, whereas it increased from 128.0 to 128.5 mmHg (0.5 increase; -1.3 to 2.3) in the control group. This change was statistically significant (P = 0.007). In contrast, the change in diastolic blood pressure did not significantly differ between the groups. In hypertensive subjects, a significant difference in systolic blood pressure reduction was seen between the groups (P = 0.032).. Moderate-intensity dietary counseling in free-living healthy subjects achieved significant dietary changes, which resulted in a significant decrease in systolic blood pressure.

Topics: Adult; Aged; Ascorbic Acid; Blood Pressure; Carotenoids; Diet, Sodium-Restricted; Feeding Behavior; Female; Fruit; Humans; Hypertension; Japan; Life Style; Middle Aged; Sodium, Dietary; Vegetables

Supplementation with antioxidant vitamins has been proposed to reduce the risk of preeclampsia and perinatal complications, but the effects of this intervention are uncertain.. We conducted a multicenter, randomized trial of nulliparous women between 14 and 22 weeks of gestation. Women were assigned to daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or placebo (microcrystalline cellulose) until delivery. Primary outcomes were the risks of maternal preeclampsia, death or serious outcomes in the infants (on the basis of definitions used by the Australian and New Zealand Neonatal Network), and delivering an infant whose birth weight was below the 10th percentile for gestational age.. Of the 1877 women enrolled in the study, 935 were randomly assigned to the vitamin group and 942 to the placebo group. Baseline characteristics of the two groups were similar. There were no significant differences between the vitamin and placebo groups in the risk of preeclampsia (6.0 percent and 5.0 percent, respectively; relative risk, 1.20; 95 percent confidence interval, 0.82 to 1.75), death or serious outcomes in the infant (9.5 percent and 12.1 percent; relative risk, 0.79; 95 percent confidence interval, 0.61 to 1.02), or having an infant with a birth weight below the 10th percentile for gestational age (8.7 percent and 9.9 percent; relative risk, 0.87; 95 percent confidence interval, 0.66 to 1.16).. Supplementation with vitamins C and E during pregnancy does not reduce the risk of preeclampsia in nulliparous women, the risk of intrauterine growth restriction, or the risk of death or other serious outcomes in their infants. (Controlledtrials.com number, ISRCTN00416244.).

Topics: Adult; Antioxidants; Ascorbic Acid; Dietary Supplements; Female; Fetal Death; Fetal Growth Retardation; Humans; Hypertension; Infant Mortality; Infant, Newborn; Infant, Small for Gestational Age; Parity; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Respiratory Distress Syndrome, Newborn; Risk; Vitamin E

The increased production of reactive oxygen species plays a role in the etiology of hypertension, but the effects of antioxidants on blood pressure are controversial. However, antioxidants possibly lower blood pressure in elderly patients with hypertension, because vascular aging is also closely related to oxidative stress. Effects of chronic treatment with ascorbic acid (CAS 50-81-7; 600 mg/day for 6 months) on blood pressure and levels of C-reactive protein, 8-isoprostane, and malondialdehyde-modified low-density lipoproteins were examined in elderly patients (n = 12, six males/six females, age 78.3 +/- 5.0 years, mean +/- SD [range, 67 to 84 years]; elderly group) and adult patients (n = 12, five males/seven females, age 54.6 +/- 6.7 years [range, 39 to 621; adult group) with refractory hypertension. Chronic treatment with ascorbic acid markedly reduced systolic blood pressure and pulse pressure in ambulatory blood pressure monitoring in the elderly group (from 154.9 +/- 21.6 to 134.8 +/- 19.7 mmHg, p < 0.001; and from 79.1 +/- 22.1 to 63.4 +/- 18.7, p < 0.05; respectively), which was accompanied by an increase in the serum levels of ascorbic acid and decreases in the levels of C-reactive protein, 8-isoprostane, and malondialdehyde-modified low-density lipoproteins. In contrast, ascorbic acid did not affect blood pressure in the adult group. These results suggest that ascorbic acid is useful for controlling blood pressure in elderly patients with refractory hypertension.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Blood Pressure; C-Reactive Protein; Female; Heart Rate; Humans; Hypertension; Lipoproteins, LDL; Male; Malondialdehyde; Middle Aged; Vitamins

There is growing evidence that oxidative stress contributes to the pathogenesis of hypertension and endothelial dysfunction. Thus, dietary antioxidants may beneficially influence blood pressure (BP) and endothelial function by reducing oxidative stress.. To determine if vitamin C and polyphenols, alone or in combination, can lower BP, improve endothelial function and reduce oxidative stress in hypertensive individuals.. A total of 69 treated hypertensive individuals with a mean 24-h ambulatory systolic blood pressure > or = 125 mmHg participated in a randomized, double-blind, placebo-controlled, factorial trial. Following a 3-week washout, participants received 500 mg/day vitamin C, 1000 mg/day grape-seed polyphenols, both vitamin C and polyphenols, or neither for 6 weeks. At baseline and post-intervention, 24-h ambulatory BP, ultrasound-assessed endothelium-dependent and -independent vasodilation of the brachial artery, and markers of oxidative damage, (plasma and urinary F2-isoprostanes, oxidized low-density lipoproteins and plasma tocopherols), were measured.. A significant interaction between grape-seed and vitamin C treatments for effects on BP was observed. Vitamin C alone reduced systolic BP versus placebo (-1.8 +/- 0.8 mmHg, P = 0.03), while polyphenols did not (-1.3 +/- 0.8 mmHg, P = 0.12). However, treatment with the combination of vitamin C and polyphenols increased systolic BP (4.8 +/- 0.9 mmHg versus placebo; 6.6 +/- 0.8 mmHg versus vitamin C; 6.1 +/- 0.9 mmHg versus polyphenols mmHg, each P < 0.0001) and diastolic BP (2.7 +/- 0.6 mmHg, P < 0.0001 versus placebo; 1.5 +/- 0.6 mmHg, P = 0.016 versus vitamin C; 3.2 +/- 0.7 mmHg, P < 0.0001 versus polyphenols). Endothelium-dependent and -independent vasodilation, and markers of oxidative damage were not significantly altered.. Although the mechanism remains to be elucidated, these results suggest caution for hypertensive subjects taking supplements containing combinations of vitamin C and polyphenols.

Topics: Antioxidants; Ascorbic Acid; Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Brachial Artery; Double-Blind Method; Drug Therapy, Combination; Endothelium, Vascular; F2-Isoprostanes; Female; Flavonoids; Humans; Hypertension; Lipoproteins, LDL; Male; Middle Aged; Oxidative Stress; Phenols; Polyphenols; Tocopherols; Ultrasonography; Vasodilation

It is not known whether the beneficial effects of N-acetylcysteine (NAC) in conditions associated with increased oxidative stress are caused by direct superoxide scavenging. We therefore compared the acute superoxide scavenging efficacy of NAC against vitamin C (VITC) on impaired endothelium-dependent vasodilation in subjects with essential hypertension.. In a cross-over randomized study, the effects of intra-arterial administration of either NAC (48 mg/min) or VITC (18 mg/min) were examined in 15 subjects with essential hypertension and in 15 normotensive control subjects. Both endothelium-dependent and endothelium-independent vasodilation were determined as forearm blood flow (FBF) response to the intra-arterial administration of acetylcholine (Ach) and sodium nitroprusside (NP) in doses of 12 and 48 mug/min and 3.2 and 12.8 mug/min, respectively.. Subjects with essential hypertension had impaired responses to both doses of Ach (Delta% FBF to higher dose of Ach: 325 +/- 146 in subjects with essential hypertension v 540 +/- 199 in control subjects; P = .02) and an impaired response to the higher dose of NP (330 +/- 108 v 500 +/- 199; P = .03). The intra-arterial administration of NAC had no effect on these responses (higher dose of Ach: 325 +/- 146 without v 338 +/- 112 with NAC, NS). In contrast, intra-arterial VITC improved both the response to Ach (320 +/- 132 without v 400 +/- 185 with VITC, P = .05) and to NP (383 +/- 162 v 447 +/- 170, P = .05).. We found that NAC showed no statistically significant effect on either endothelium-dependent or endothelium-independent vasodilation in hypertensive subjects, whereas VITC did. We conclude that NAC is therefore not an effective superoxide scavenger in vivo. Other, nonimmediate effects such as the generation of glutathione may explain the beneficial effects of NAC in conditions associated with oxidative stress.

Topics: Acetylcholine; Acetylcysteine; Adult; Ascorbic Acid; Blood Flow Velocity; Endothelium, Vascular; Female; Forearm; Free Radical Scavengers; Humans; Hypertension; Infusions, Intra-Arterial; Male; Middle Aged; Nitroprusside; Superoxides; Vasodilation; Vasodilator Agents

Hypertension is considered resistant if blood pressure cannot be reduced to <140/90 mmHg with an appropriate triple-drug regimen, including an oral diuretic, with all agents administered at maximal dosages. This definition has evolved with the development of new therapies and evidence-based data supporting treatment to lower BP goals.. To assess whether vitamin C and atorvastatin improve endothelial function and blood pressure control in subjects with resistant arterial hypertension and dyslipidemia.. Forty-eight hyperlipidemic subjects with RH (office systolic BP >140 mmHg and/or office diastolic BP >90 mmHg notwithstanding antihypertensive treatment with three medications in maximal doses) were randomized into three groups to receive additional medication for 8 weeks. Group VTC (n = 17)--mean 24 hour SBP 150.6 +/- 5.2 mmHg, DBP 86.1 +/- 3.3 mmHg, low density lipoprotein 158.1 +/- 24.5 mg/dl--received vitamin C 500 mg per day; Group ATR (n = 15)--mean 24 hour SBP 153.1 +/- 4.8 mmHg, DBP 87.1 +/- 6.7 mmHg, LDL 162.6 +/- 13.6 mg/dl--received atorvastatin 20 mg/day; and Group PLA (n = 16)--mean 24 hour SBP 151.1 +/- 7.4 mmHg, DBP 84.8 +/- 5.9 mmHg, LDL 156.7 +/- 26.1 mg/dl--received a placebo. High resolution ultrasound was used to calculate brachial artery flow-mediated dilation, and 24 hour ambulatory BP monitoring was performed at study entry and after 8 weeks.. In the ATR group there were significant reductions of SBP (deltaSBP1-2: 13.7 +/- 5.6 mmHg, P 0.001), DBP (deltaDBP1-2: 7.8 +/- 5.7 mmHg, P 0.01), LDL (deltaLDL1-2: 67.7 +/- 28.3 mg/dl, P < 0.001) and improvement of brachial artery FMD (deltaFMD2-1: 4.2 +/- 2.6%). No significant changes in BP, LDL and FMD were observed in the other two groups.. In subjects with RH and dyslipidemia, atorvastatin 20 mg/day compared to vitamin C 500 mg/day may help to achieve better BP control and improve endothelial function in a finite period. A larger trial is needed to assess the drug's efficacy in this population for longer periods.

Topics: Anticholesteremic Agents; Antihypertensive Agents; Ascorbic Acid; Atorvastatin; Blood Pressure; Brachial Artery; Cross-Sectional Studies; Endothelium, Vascular; Female; Heptanoic Acids; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Pyrroles

Essential hypertension is associated with impaired endothelium-dependent vasodilation caused by oxidative stress-induced nitric oxide (NO) breakdown and compensatory production of a hyperpolarizing factor. To test whether calcium antagonist treatment can restore NO availability and prevent hyperpolarization through antioxidant properties, in 15 healthy subjects and 15 patients with essential hypertension, we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial bradykinin (5, 15, 50 ng/100 mL per minute), an endothelium-dependent vasodilator, in basal conditions, during infusion of NG-monomethyl-l-arginine (L-NMMA, 100 microg/100 mL per minute), an NO-synthase inhibitor, and ouabain (0.72 microg/100 mL per minute), an Na+-K+ ATPase inhibitor to prevent hyperpolarization. These infusions were repeated in the presence of the antioxidant vitamin C (8 mg/100 mL/min). The response to sodium nitroprusside was also evaluated. In controls, vasodilation to bradykinin was inhibited by L-NMMA and remained unchanged by ouabain or vitamin C. In hypertensive patients, vasodilation to bradykinin was blunted and resistant to L-NMMA but sensitive to ouabain. Vitamin C increased the response to bradykinin and restored the inhibiting effect of L-NMMA while preventing the effect of ouabain. In hypertensive patients, infusions were repeated after 3-month treatment with lercanidipine (10 to 20 mg daily). Lercanidipine decreased plasma lipoperoxides, isoprostanes, and malondialdehyde and increased plasma antioxidant capacity. Moreover, lercanidipine increased the vasodilation to bradykinin and restored the inhibiting effect of L-NMMA on bradykinin-induced vasodilation while preventing the effect of ouabain. Finally, vitamin C no longer exerted its facilitating activity. These results indicate that in essential hypertension, lercanidipine increases endothelium-dependent vasodilation by restoring NO availability and preventing hyperpolarization, an effect probably determined by antioxidant activity.

Topics: Antioxidants; Ascorbic Acid; Calcium Channel Blockers; Dihydropyridines; Endothelium, Vascular; Female; Forearm; Humans; Hypertension; Male; Middle Aged; Nitric Oxide; Oxidative Stress; Regional Blood Flow; Vasodilation

The effect of oxidative stress on endothelial function, platelet function, and fibrinolysis in hypertension with or without glucose intolerance was examined. The endothelium, platelets and fibrinolysis play important roles in the progression of atherosclerosis and interact with each other. We have previously demonstrated that glucose intolerance impairs endothelial function in hypertension, but its precise mechanisms have not been clarified. Hypertensive patients were divided by the results of 75-g oral glucose tolerance test into a normal glucose metabolism group (n = 65) and a glucose intolerance group (n = 47). The plasma level of thiobarbituric acid-reactive substances (TBARS) was assessed as a marker of oxidative stress. Endothelial function was assessed by flow-mediated dilatation (FMD), platelet function by the concentration of ADP dose inducing half-maximal aggregation (EC50), and fibrinolytic parameters by radioimmunoassay. These functions were assessed before and after acute administration of vitamin C. FMD was reduced while TBARS and fibrinolytic parameters were higher in patients with glucose intolerance than in those with a normal glucose metabolism. Vitamin C increased FMD and reduced fibrinolytic parameters significantly in the glucose intolerance group, but not in the group with normal glucose metabolism. On the other hand, the EC50 was similar in both groups. In conclusion, glucose intolerance aggravates oxidative stress, thereby contributing to the impairment of endothelial function in patients with hypertension. These abnormalities affect fibrinolysis but not platelet function.

Topics: Adult; Ascorbic Acid; Blood Platelets; Endothelium, Vascular; Female; Fibrinolysis; Glucose Intolerance; Glucose Tolerance Test; Humans; Hypertension; Lipids; Male; Oxidative Stress; Platelet Function Tests; Smoking; Thiobarbituric Acid Reactive Substances

Plasma vitamin A, C and E levels and erythrocyte antioxidant enzyme activities were investigated in type I and type II diabetic subjects with and without complications, i.e., hypertension, coronary artery disease and renal failure. Reverse phase HPLC was used to quantify vitamin A and E levels. We observed that the vitamin C levels were not significantly different between control and diabetic subjects. However, vitamin A and E levels were significantly lower in type I and type II diabetic subjects compared to controls. Superoxide dismutase (SOD) activity was significantly lower in type II, but not in type I, diabetic patients compared to controls. Interestingly, glutathione reductase and peroxidase activities were diminished in type I, but not in type II, diabetic subjects as compared to controls. Catalase activity was lower in both types of diabetic patients in comparison with their respective controls. Altogether these results suggest that diabetes mellitus may be associated with altered antioxidant status regardless to various complications.

Topics: Adult; Antioxidants; Ascorbic Acid; Catalase; Chromatography, High Pressure Liquid; Coronary Artery Disease; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Erythrocytes; Female; Glutathione Peroxidase; Glutathione Reductase; Humans; Hypertension; Male; Middle Aged; Renal Insufficiency; Superoxide Dismutase; Vitamin A; Vitamin E; Vitamins

At 60 patients with coronary artery disease and high blood pressure studied effects of a diet with low lipid and flavons. The application of a diet and flavons promoted positive dynamics (changes) of clinical manifestations of disease, lipid spectrum and antioxidants.

Topics: Adult; Aged; Antioxidants; Arteriosclerosis; Ascorbic Acid; Cardiovascular Diseases; Diet; Electrocardiography; Flavonoids; Humans; Hypertension; Lipid Peroxidation; Malondialdehyde; Middle Aged; Myocardial Ischemia; Obesity

We sought to determine whether abnormal myocardial blood flow (MBF) responses to the cold pressor test (CPT) in patients with various risk factors may involve different mechanisms that could lead to varying responses of short- and long-term administration of antioxidants.. There is a growing body of evidence that increased vascular production of reactive oxygen species markedly reduces the bioavailability of endothelium-derived nitric oxide, leading to impaired vasodilator function. It is unknown whether increased oxidative stress is the prevalent mechanism underlying endothelial dysfunction in patients with different coronary risk factors.. Fifty patients with normal coronary angiograms were studied. The MBF responses to CPT was determined by means of positron emission tomography before and after intravenous infusion of 3 g vitamin C or saline (placebo), as well as after 3 months and 2 years of 2 g vitamin C or placebo supplementation daily.. In hypertensive patients, the change in MBF (DeltaMBF) was not modified significantly by short-term vitamin C administration challenges (0.20 +/- 0.20 ml/g/min; p = NS) but was significantly increased after three months and two years of treatment with vitamin C versus baseline (0.58 +/- 0.27 and 0.63 +/- 0.17 vs. 0.14 +/- 0.18 ml/g/min; both p < or = 0.001). In smokers, DeltaMBF in response to CPT was significantly increased after short-term vitamin C infusion and long-term vitamin C treatment (0.52 +/- 0.10, 0.54 +/- 0.13, 0.50 +/- 0.07 vs. -0.08 +/- 0.10 ml/g/min; all p < or = 0.001). In hypercholesterolemic patients, no improvement in DeltaMBF during CPT was observed after short- and long-term vitamin C treatment (0.05 +/- 0.14, 0.08 +/- 0.18, 0.02 +/- 0.19 vs. 0.08 +/- 0.16 ml/g/min; p = NS). The CPT-induced DeltaMBF in hypertensive patients and smokers after follow-up was significant as compared with placebo and control subjects (p < or = 0.001).. The present study revealed marked heterogeneous responses in MBF changes to short- and long-term vitamin C treatment in patients with various risk factors, which highlights the quite complex nature underlying abnormal coronary vasomotion.

Topics: Antioxidants; Ascorbic Acid; Coronary Angiography; Coronary Circulation; Coronary Disease; Coronary Vessels; Female; Follow-Up Studies; Humans; Hypercholesterolemia; Hypertension; Infusions, Intravenous; Male; Middle Aged; Oxidative Stress; Reactive Oxygen Species; Risk Factors; Smoking; Tomography, Emission-Computed; Treatment Outcome; Vasoconstriction; Vasodilation

The endothelium plays an important role in maintaining vascular tone and function. Essential hypertension is associated with alterations in endothelial function. The effects of antihypertensive agents on endothelial function have not been fully evaluated in human hypertension and data on the forearm circulation of humans are controversial. The aim of this study was to determine whether treatment with an angiotensin converting enzyme (ACE) inhibitor or a calcium antagonist improves endothelial dysfunction in hypertensive patients and whether the mechanism involved could be related to antioxidant activity. Endothelial function was estimated using venous occlusion plethysmography in 18 hypertensive patients and 11 healthy volunteers. The patients in the hypertension group were treated with enalapril or amlodipine. The change of forearm blood flow (FBF) was measured during acetylcholine infusion through the brachial artery and also during intra-arterial vitamin C infusion to explore the effects of vitamin C on responses to acetylcholine. FBF response to acetylcholine was significantly enhanced by intra-arterial infusion of vitamin C in the hypertensive group before antihypertensive treatment. Co-infusion of L-NMMA(N(G)-monomethyl-L-arginine), an inhibitor of nitric oxide synthase, blunted forearm blood flow response to acetylcholine. After antihypertensive treatment with enalapril or amlodipine for 2 months in the hypertensive group, endothelium-dependent vasorelaxation (vasodilatory response to acetylcholine) was significantly improved. Even though the mechanisms leading to depressed endothelial function in essential hypertension remain to be elucidated, our study shows that treatment with an ACE inhibitor or a calcium antagonist resulted in demonstrable improvement by a mechanism that is probably related to antioxidant activity.

Topics: Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Ascorbic Acid; Calcium Channel Blockers; Enalapril; Endothelium, Vascular; Female; Forearm; Humans; Hypertension; Male; Middle Aged; Nitroprusside; omega-N-Methylarginine; Regional Blood Flow

Presentation, response to therapy, and clinical outcome in hypertension differ according to race, and these observations could relate to differences in microvascular function. We examined forearm microvascular function in age-matched black (n=56) and white subjects (n=62) using intra-arterial agonist infusion and venous occlusion plethysmography. In normotensive subjects (n=70; 34 black and 36 white normotensives), methacholine-, sodium nitroprusside-, and verapamil-induced vasodilation was equivalent in black and white subjects. In hypertensive subjects (n=48; 22 black and 26 white hypertensives), the vasodilator response to methacholine was markedly lower in black subjects compared with white subjects (P<0.001). The vasodilator responses to sodium nitroprusside and verapamil, however, were equivalent in black and white hypertensive subjects. Acute ascorbic acid infusion improved the methacholine response equally in black and white hypertensive patients, suggesting that a difference in a rapidly reversible form of oxidative stress does not explain these findings. Thus, the present study demonstrates important racial differences in vascular function and a marked impairment in endothelial vasomotor function in black patients with hypertension. Further studies will be required to elucidate the mechanisms and determine whether these insights will lead to more appropriately tailored management of hypertension and its complications.

Topics: Adult; Analysis of Variance; Antioxidants; Ascorbic Acid; Black People; Brachial Artery; Bronchoconstrictor Agents; Dose-Response Relationship, Drug; Female; Forearm; Humans; Hypertension; Male; Methacholine Chloride; Middle Aged; Nitroprusside; Regional Blood Flow; Vascular Resistance; Vasodilator Agents; Verapamil; White People

The effects of antihypertensive agents on endothelial function have not been fully evaluated in human hypertension and data on the forearm circulation of humans are controversial. The aim of this study was (1) to evaluate the endothelial function in hypertensive patients (2) to investigate whether vitamin C administration has any benefit on the endothelial function and (3) to determine whether treatment with calcium antagonist improves endothelial dysfunction in hypertensive patients.. The endothelial function was estimated using venous occlusion plethysmography (VOP) in 8 hypertensive patients and 8 healthy volunteers. The patients in the hypertension group were treated with amlodipine, then examined again. The change of forearm blood flow (FBF) was measured with acetylcholine infusion through brachial artery and also with intra-arterial vitamin C.. Forearm blood flow response to acetylcholine was significantly enhanced with intra-arterial infusion of vitamin C in hypertensive group before antihypertensive treatment. Co-infusion of L-NMMA, an inhibitor of nitric oxide synthase, blunted forearm blood flow response to acetylcholine. After treatment with amlodipine for 2 months in hypertensive group, endothelium-dependent vasorelaxation to acetylcholine was significantly improved compared to pretreatment, and vitamin C did not affect the improved endothelial function by amlodipine treatment.. Vitamin C (acutely) and amlodipine (chronically) improved endothelial function in hypertensive patients. These results suggest that increased oxidative stress, at least in part, may be involved in the decreased endothelial function in hypertension.

Topics: Adult; Aged; Amlodipine; Antihypertensive Agents; Ascorbic Acid; Calcium Channel Blockers; Endothelium, Vascular; Enzyme Inhibitors; Female; Humans; Hypertension; Male; Middle Aged; Nitric Oxide Synthase; omega-N-Methylarginine; Vasodilation

In a double-blinded randomized controlled trial, we investigated the long-term effect of vitamin C supplementation on blood pressure. A total of 439 Japanese subjects with atrophic gastritis initially participated in the trial using vitamin C and beta-carotene to prevent gastric cancer. Before and on early termination of beta-carotene supplementation, 134 subjects dropped out of this trial, whereas 120 and 124 subjects took the vitamin C supplement daily at either 50 mg or 500 mg, respectively, for 5 years. Before supplementation, neither systolic nor diastolic blood pressure was significantly related with the serum vitamin C concentration. This relationship was unchanged after adjustment for age, body mass index, and alcohol intake or after stratification by gender. After 5 years, systolic blood pressure significantly increased in groups, regardless of vitamin C dose, compared with baseline. Systolic blood pressure in the high-dose group (500 mg daily) increased from 125.4 to 131.7 mm Hg (5.88 mm Hg increase; 95% confidence interval [CI], 3.11 to 8.65). This value was similar with that of the low-dose group (5.73 mm Hg increase; 95% CI, 2.62 to 8.83) and of the dropout group (4.52 mm Hg increase; 95% CI, 1.26 to 7.77). There was no difference in change of diastolic blood pressure among the 3 groups. In conclusion, we observed no reduction in blood pressure with long-term moderate doses (500 mg/day) of vitamin C supplementation in a high-risk population for stomach cancer and stroke.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Blood Pressure; Diastole; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Gastritis, Atrophic; Humans; Hypertension; Japan; Male; Middle Aged; Stomach Neoplasms; Systole; Time; Treatment Outcome

Hypertension is associated with low plasma ascorbic acid levels and impaired endothelial function. Recent evidence suggests that increased vascular oxidative stress contributes to the pathophysiology of endothelial dysfunction and hypertension. We recently showed that chronic oral ascorbic acid therapy lowers blood pressure in hypertensive patients. We hypothesized that it would also improve endothelial vasomotor function. In a randomized, double-blind, placebo-controlled study, we examined the effect of acute (2 g po) and chronic (500 mg/day for 1 mo) ascorbic acid treatment on brachial artery flow-mediated dilation in 39 patients with hypertension. Compared with 82 age- and gender-matched normotensive controls, these patients had impaired endothelium-dependent, flow-mediated dilation of the brachial artery [8.9 +/- 6.1 vs. 11.2 +/- 5.7% (SD), P < 0.04]. After therapy, plasma ascorbic acid concentrations increased acutely from 50 +/- 12 to 149 +/- 51 micromol/l and were maintained at 99 +/- 33 micromol/l with chronic treatment (both P < 0.001). As previously reported, chronic ascorbic acid therapy reduced systolic and mean blood pressure in these patients. However, acute or chronic ascorbic acid treatment had no effect on brachial artery endothelium-dependent, flow-mediated dilation or on endothelium-independent, nitroglycerin-mediated dilation. These results demonstrate that conduit vessel endothelial dysfunction secondary to hypertension is not reversed by acute or chronic treatment with oral ascorbic acid. The effects of this treatment on resistance vessel vasomotor function warrant further investigation.

Topics: Adult; Antioxidants; Ascorbic Acid; Brachial Artery; Cohort Studies; Cyclic GMP; Eicosanoids; Endothelium, Vascular; Female; Humans; Hypertension; Male; Middle Aged; Nitric Oxide; Regional Blood Flow; Vasodilation

We studied the effect of an antioxidant, the intracoronary infusion of vitamin C, on basal and dobutamine-stimulated left ventricular (LV) contractility.. Nineteen patients with normal ventricular function participated in this study. A micromanometer-tipped catheter was inserted into the LV. In the experimental group (n=10), an infusion catheter was positioned in the left main coronary artery. LV peak +dP/dt (LV +dP/dt) was measured in response to the intravenous infusion of dobutamine before (Dob) and during (Dob+vit C) the intracoronary infusion of vitamin C. The intracoronary infusion of vitamin C had no effect on basal LV +dP/dt or any other hemodynamic parameter. The infusion of vitamin C augmented the LV +dP/dt response to dobutamine by 22+/-4% (Dob, 1680+/-76 mm Hg/s; Dob+vit C, 1814+/-97 mm Hg/s, P<0.01). In the control group (n=9), LV +dP/dt was measured in response to sequential infusions of dobutamine (Dob, Dob-2) given at the same time intervals as in the experimental group but without the intracoronary infusion of vitamin C. In contrast to the experimental group, no difference in LV +dP/dt was observed between the 2 infusions of dobutamine (Dob, 1706+/-131 mm Hg/s; Dob-2, 1709+/-138 mm Hg/s, P=NS).. The administration of the antioxidant vitamin C augments the inotropic response to dobutamine in humans. This suggests that redox environment contributes to the adrenergic regulation of ventricular contractility.

Topics: Adrenergic beta-Agonists; Antioxidants; Ascorbic Acid; Cardiac Catheterization; Cardiotonic Agents; Coronary Disease; Coronary Vessels; Diabetes Mellitus, Type 2; Dobutamine; Drug Synergism; Female; Hemodynamics; Humans; Hypertension; Infusions, Intra-Arterial; Male; Middle Aged; Myocardial Contraction; Oxidation-Reduction; Ventricular Function, Left

Topics: Administration, Oral; Antioxidants; Ascorbic Acid; Blood Pressure; Female; Humans; Hypertension; Male; Middle Aged; Nitric Oxide; Respiration

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Blood Pressure; Double-Blind Method; Humans; Hypertension; Prospective Studies; Vitamin E

To determine the effect of oral vitamin C supplements on ambulatory blood pressure and plasma lipids.. A 6-month double-blind randomized placebo-controlled cross-over study with a 1 -week washout between cross-over periods.. Vitamin C 500 mg daily or matching placebo was given to 40 men and women aged between 60 and 80 years for 3 months each in a cross-over fashion. Clinic and 24-h ambulatory blood pressure, plasma ascorbate and lipids were measured at baseline and at the end of each cross-over phase.. Clinic blood pressure did not change between placebo and vitamin C phases. Daytime ambulatory blood pressure showed a small but significant fall in systolic blood pressure (2.0 +/- 5.2 mmHg; 95% confidence interval 0-3.9 mmHg) but not in diastolic blood pressure. Regression analysis showed that with increasing baseline daytime blood pressure the fall in blood pressure with vitamin C supplementation increased. Regression analysis of the change in high-density lipoprotein (HDL) cholesterol showed a significant effect of sex on the change in HDL cholesterol. In women, but not men, HDL cholesterol increased significantly by 0.08 +/- 0.11 mmol/l, P=0.007. There was no change in low-density lipoprotein cholesterol between treatment periods.. In older adults high intakes of ascorbic acid have modest effects on lowering high systolic blood pressure, which could contribute to the reported association between higher vitamin C intake and lower risk of cardiovascular disease and stroke.

Topics: Aged; Aged, 80 and over; Aging; Ascorbic Acid; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypertension; Lipids; Male; Reference Values; Systole

In a randomised, double-blind, placebo-controlled study we showed that treatment of hypertensive patients with ascorbic acid lowers blood pressure. Further studies of ascorbic acid to treat hypertension, with clinical endpoints, are warranted.

Topics: Adult; Aged; Ascorbic Acid; Blood Pressure; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Reactive Oxygen Species; Treatment Outcome

Essential hypertension is associated with impaired endothelium-dependent vasodilation. Inactivation of endothelium-derived nitric oxide by oxygen free radicals participates in endothelial dysfunction in experimental hypertension. To test this hypothesis in humans, we evaluated the effect of antioxidant vitamin C on endothelium-dependent responses in essential hypertensive patients.. In 14 healthy subjects (47.1+/-4.8 years; blood pressure, 120.6+/-4.5/80.9+/-3.5 mm Hg) and 14 essential hypertensive patients (47.3+/-5.1 years; blood pressure, 153.9+/-7.1/102.3+/-4.1 mm Hg), we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg x 100 mL(-1) x min(-1)) or sodium nitroprusside (1, 2, and 4 microg/100 mL forearm tissue per minute), an endothelium-dependent and -independent vasodilator, respectively, in basal conditions and during infusion of intrabrachial vitamin C (2.4 mg/100 mL forearm tissue per minute). In hypertensive patients but not in control subjects, vitamin C increased (P<0.01) the impaired vasodilation to acetylcholine, whereas the response to sodium nitroprusside was unaffected. Moreover, in another 14 hypertensive patients (47.1+/-5.2 years; blood pressure, 155.2+/-6.9/103.7+/-4.5 mm Hg), the facilitating effect of vitamin C on vasodilation to acetylcholine was reversed by N(G)-monomethyl-L-arginine (100 microg/100 mL forearm tissue per minute), a nitric oxide synthase inhibitor, suggesting that in essential hypertension superoxide anions impair endothelium-dependent vasodilation by nitric oxide breakdown. Finally, because in adjunctive 7 hypertensive patients (47.8+/-6.1 years; blood pressure, 155.3+/-6.8/103.5+/-4.3 mm Hg), indomethacin (50 microg/100 mL forearm tissue per minute), a cyclooxygenase inhibitor, prevented the potentiating effect of vitamin C on vasodilation to acetylcholine, it is possible that in essential hypertension a main source of superoxide anions could be the cyclooxygenase pathway.. In essential hypertensive patients, impaired endothelial vasodilation can be improved by the antioxidant vitamin C, an effect that can be reversed by the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine. These findings support the hypothesis that nitric oxide inactivation by oxygen free radicals contributes to endothelial dysfunction in essential hypertension.

Topics: Acetylcholine; Adult; Antioxidants; Ascorbic Acid; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Endothelium, Vascular; Enzyme Inhibitors; Female; Humans; Hypertension; Indomethacin; Male; Middle Aged; Nitric Oxide; omega-N-Methylarginine; Vasodilation

1. Hypertension affects 30% of adults and low intakes of antioxidants have been associated with increased risk of hypertension and cardiovascular disease. To investigate the effect of short-term high-dose antioxidant supplementation on blood pressure in hypertensive and normotensive outpatients, we undertook a randomized, double-blind, crossover design placebo-controlled study. 2. Forty subjects were recruited from medical outpatient clinics, of whom 38 completed the study. Twenty-one were attending for treatment of hypertension and 17 were normotensive, attending for minor gastrointestinal complaints. Subjects were randomly assigned to receive either 8 weeks placebo followed by 2 weeks washout then 8 weeks antioxidants or vice versa. The combination of antioxidants consisted of 200 mg of zinc sulphate, 500 mg of ascorbic acid, 600 mg of alpha-tocopherol (sodium succinate salt) and 30 mg of beta-carotene daily. 3. Systolic blood pressure fell at the end of the antioxidant phase compared with the placebo phase both in subjects receiving anti-hypertensive therapy (P < 0.01) and those who were normotensive (P = 0.067). Circulating levels of beta-carotene and alpha-tocopherol increased in all subjects during supplementation (P < 0.01) and urine nitrite increased in hypertensive patients (P < 0.05). 4. Short-term oral high-dose combination antioxidant therapy reduces blood pressure, possibly via increased availability of nitric oxide. This study may have implications for the innovative use of antioxidants as an adjunct to anti-hypertensive therapy.

Topics: Administration, Oral; Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Blood Pressure; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Humans; Hypertension; Middle Aged; Nitric Oxide; Nitrites; Vitamin E; Zinc Sulfate

There is evidence for increased formation of free radicals in patients with hypertension, raising the possibility that NO is inactivated by free radicals, which impairs coronary endothelial function. Therefore, we tested the hypothesis that the antioxidant vitamin C could improve abnormal endothelial function of coronary arteries in patients with hypertension.. In 22 hypertensive patients without relevant coronary artery stenoses, endothelium-dependent vascular responses of the left anterior descending coronary artery (LAD) to acetylcholine (0.01, 0.1, and 1.0 micromol/L) were determined before and immediately after intravenous infusion of 3 g vitamin C (17 patients) or placebo (5 patients). In a subgroup of 10 patients, papaverine-induced flow-dependent vasodilation (FDD) was measured before and after vitamin C (5 patients) or placebo (5 patients) infusion. Segmental responses of the coronary artery luminal area were analyzed with quantitative coronary angiography. Before vitamin C infusion, the mean changes of LAD luminal areas at increasing doses of acetylcholine were -6.1+/-2.2%, -15.2+/-4.9%, and -33.9+/-8.1% (negative numbers symbolize vasoconstriction) and during FDD, 5.4+/-1.0%. The vasoconstrictor response during acetylcholine was reduced and FDD was augmented by vitamin C. After vitamin C infusion, LAD luminal areas changed by -3.2+/-2.3%, -5.8+/-3.6%, and -10.2+/-5.6% (P<.05, acetylcholine) and 17.8+/-2.8% (P<.05, FDD). Doppler flow velocity (during baseline, acetylcholine, and FDD) was not significantly affected by vitamin C.. Vitamin C improves the endothelium-dependent vasomotor capacity of coronary arteries in patients with hypertension and patent coronary arteries. These findings suggest that increased oxidative stress contributes to endothelial dysfunction in hypertensive patients.

Topics: Acetylcholine; Adult; Aged; Antioxidants; Arteries; Ascorbic Acid; Coronary Vessels; Drug Therapy, Combination; Endothelium, Vascular; Female; Humans; Hypertension; Male; Middle Aged; Papaverine; Pericardium; Vasodilator Agents

We have investigated the effect on blood pressure of treatment with vitamin C (an antioxidant and free radical scavenger) in patients with both systolic and essential hypertension. Following a 2-week run-in phase, two age- and sex-matched groups of untreated hypertensive subjects were randomised in a double-blind study to receive 6 weeks' oral treatment with either vitamin C, 250 mg twice daily (n = 22; 8M/14F, mean age 73.7 +/- 4.9 years) or placebo, one capsule twice daily (n = 26; 10M/16F, mean age 73.8 +/- 5.3 years). Blood pressure was measured in the sitting position using a random zero sphygmomanometer on three occasions during the run-in phase, and again at 2, 4 and 6 weeks after commencing treatment. Venous blood samples for measurement of plasma ascorbic acid (AA) and lipid peroxides (LP) were measured in all subjects at baseline and at 4 and 6 weeks after the start of vitamin C or placebo treatment. During the study period, significant falls in both systolic (vitamin C group, mean change -10.3 (95% CI 0.7-20.0) mm Hg, p = 0.05) and diastolic (vitamin C group, mean change -5.9 (95% CI 0.2-11.5) mm Hg, p = 0.03; placebo group, mean change -4.7 (95% CI 0.3-9.1) mm Hg, p = 0.05) blood pressure occurred. However, no statistical difference between the effects of either treatment on blood pressure was observed. At baseline, AA concentrations were lower in the vitamin C-treated group compared with the placebo group (44.6 +/- 2.4 vs. 57.7 +/- 4.2 mumol/l, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Ascorbic Acid; Blood Pressure; Diastole; Double-Blind Method; Female; Humans; Hypertension; Lipid Peroxides; Male; Systole

Topics: Adult; Antioxidants; Ascorbic Acid; Blood Pressure; Cardiovascular Diseases; Female; Free Radicals; Heart Rate; Humans; Hypertension; Male; Middle Aged; Reactive Oxygen Species; Smoking

Topics: Aged; Aged, 80 and over; Aging; Ascorbic Acid; Blood Pressure; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged

1. In this study an acute anti-hypertensive effect of three anti-oxidant agents (vitamin C, thiopronine and glutathione) in hypertensive subjects and in both hypertensive and non-hypertensive diabetic patients is reported. 2. The anti-oxidants had no effect on blood pressure in healthy normal subjects at a dose of 6 mmol, but thiopronine and glutathione produced a significant hypotensive effect at a dose of 12 mmol. 3. These data suggest that anti-oxidants might have a dilatatory effect and that an imbalance of the nitric oxide-free radical interaction might facilitate the development of hypertension in humans.

Topics: Adult; Antioxidants; Ascorbic Acid; Diabetes Mellitus, Type 1; Double-Blind Method; Drug Administration Schedule; Female; Glutathione; Heart Rate; Humans; Hypertension; Injections, Intravenous; Male; Middle Aged; Tiopronin

Topics: Adult; Aged; Ascorbic Acid; Clinical Trials as Topic; Diuretics; Female; Flavonoids; Humans; Hypertension; Magnesium; Male; Middle Aged; Phytotherapy; Plants, Medicinal; Rauwolfia

There is no dietary strategy that has yet been specifically advocated for haemophilia. Therefore, we sought to assess the effect of the Dietary Approaches to Stop Hypertension (DASH) diet in adolescents with haemophilia. In this parallel trial, forty male adolescents with haemophilia were dichotomised into the DASH group or control group for 10 weeks. The serum high sensitivity C-reactive protein, IL-6, complete blood count (CBC), serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, partial thromboplastin time (PTT), waist circumference (WC), percentage of body fat, fat-free mass and liver steatosis were measured at the beginning and end of the study. Serum vitamin C was measured as a biomarker of compliance with the DASH diet. The DASH diet was designed to include high amounts of whole grains, fruits, vegetables and low-fat dairy products, as well as low amounts of saturated fats, cholesterol, refined grains, sweets and red meat. Serum vitamin C in the DASH group was significantly increased compared with the control (

Topics: Adolescent; Ascorbic Acid; Blood Cell Count; Body Composition; Child; Dietary Approaches To Stop Hypertension; Hemophilia A; Humans; Hypertension; Inflammation; Liver; Male; Prothrombin Time

Excessive oxidative stress is associated with hypertension in professional high-temperature working conditions. Polyphenols exhibit a cardioprotective effect. Hawthorn contains high amounts of flavonoids, though its effect on hypertension protection has yet to be studied. This study aims to investigate this effect of extract of hawthorn (EH) or its combination with vitamin C (Vit. C) in rats induced by working under a hot environment.. Forty-two male rats were randomly divided into a control group under normal temperature and six treatment groups exposed at 33 ± 1 °C along with 1 h of daily treadmill running. They were orally provided with water, Vit. C (14mg/kg), EH (125, 250, and 500 mg/kg), and EH500 + Vit. C, once a day for four weeks.. Both EH and Vit. C alone reduced the systolic and diastolic blood pressure of rats exposed to the heat environment; however, their joint supplementation completely maintained their blood pressure to the normal level throughout the experimental period. No morphological changes were found on the intima of aorta. Moreover, the co-supplementation of EH and Vit. C prevented the changes of heat exposure in inducing oxidative stress markers, such as glutathione peroxidase, catalase, total antioxidant capacity, and nitric oxide; the synergistic action was more effective than either individual treatment of EH and Vit. C. Furthermore, the administration of EH had more potent effects on increasing superoxide dismutase, IL-2, the 70 kilodalton heat shock proteins and high sensitivity C reactive protein, and decreasing serum malondialdehyde and lipofuscin in vascular tissue than those in Vit. C group.. A strong synergistic effect of EH and Vit. C on the prevention of hypertension under heat exposure was established, as they inhibited the oxidative stress state. This study also sets up a novel intervention strategy in animal models for investigation on the early phases of hypertension induced by heat exposure.

Topics: Animals; Ascorbic Acid; Crataegus; Flavonoids; Heat Stress Disorders; Hypertension; Male; Rats; Rats, Sprague-Dawley

The rostral ventrolateral medulla (RVLM) is the main sympathetic output of the central nervous system to control blood pressure. Reportedly, reactive oxygen species (ROS) can increase arterial pressure, leading to hypertension. As ROS increase the sympathetic tone in RVLM and obese animals present grater oxidative stress, it would be important to note this relationship.. Therefore, we evaluated the systemic and central effects (in the RVLM) of vitamin C (vit C, an antioxidant) on the redox balance and cardiovascular and autonomic profiles in hyperadipose male rats. We also evaluated the neurotransmission by L-glutamate (L-glu) and vit C in the RVLM of awake hyperadipose rats.. Our study confirmed that hyperadipose rats were hypertensive and tachycardic, presented increased sympathetic and decreased parasympathetic modulation of the heart, and had increased plasma lipoperoxidation compared with the control rats (CTR). Oral vitamin C treatment reverted cardiovascular, autonomic, and plasma redox dysfunction. Hyperadipose rats presented a higher blood pressure increase after L-glu microinjection and a lower response to vit C in the RVLM compared with the CTR group. Biochemical analysis of redox balance in RVLM punches showed that hyperadipose rats have increased NBT and T-BARS, and after treatment with vit C, the oxidative profile decreased. The antioxidative activity of vit C reduced the amount of ROS in the RVLM area that might have resulted in lowered blood pressure and sympathetic modulation.. Our data suggest central and peripheral benefits of vit C treatment on cardiovascular, autonomic, and oxidative dysfunctions in hyperadipose animals.

Topics: Animals; Antioxidants; Ascorbic Acid; Autonomic Nervous System; Blood Pressure; Cardiovascular System; Heart Rate; Hypertension; Male; Medulla Oblongata; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species; Superoxide Dismutase; Sympathetic Nervous System

Defined by dysfunction or degeneration of Aδ and C fibers, small fiber neuropathies (SFNs) entail a relevant health burden. In 50% of cases, the underlying cause cannot be identified or treated. In 100 individuals (70% female individuals; mean age: 44.8 years) with an idiopathic, skin biopsy-confirmed SFN, we characterized the symptomatic spectrum and measured markers of oxidative stress (vitamin C, selenium, and glutathione) and inflammation (transforming growth factor beta, tumor necrosis factor alpha), as well as neurotoxic 1-deoxy-sphingolipids. Neuropathic pain was the most abundant symptom (95%) and cause of daily life impairment (72%). Despite the common use of pain killers (64%), the painDETECT questionnaire revealed scores above 13 points in 80% of patients. In the quantitative sensory testing (QST), a dysfunction of Aδ fibers was observed in 70% and of C fibers in 44%, affecting the face, hands, or feet. Despite normal nerve conduction studies, QST revealed Aβ fiber involvement in 46% of patients' test areas. Despite absence of diabetes mellitus or mutations in SPTLC1 or SPTLC2 , plasma 1-deoxy-sphingolipids were significantly higher in the sensory loss patient cluster when compared with those in patients with thermal hyperalgesia ( P < 0.01) or those in the healthy category ( P < 0.1), correlating inversely with the intraepidermal nerve fiber density (1-deoxy-SA: P < 0.05, 1-deoxy-SO: P < 0.01). Patients with arterial hypertension, overweight (body mass index > 25 kg/m 2 ), or hyperlipidemia showed significantly lower L-serine (arterial hypertension: P < 0.01) and higher 1-deoxy-sphingolipid levels (arterial hypertension: P < 0.001, overweight: P < 0.001, hyperlipidemia: P < 0.01). Lower vitamin C levels correlated with functional Aβ involvement ( P < 0.05). Reduced glutathione was lower in patients with Aδ dysfunction ( P < 0.05). Idiopathic SFNs are heterogeneous. As a new pathomechanism, plasma 1-deoxy-sphingolipids might link the metabolic syndrome with small fiber degeneration.

Topics: Adult; Ascorbic Acid; Female; Humans; Hypertension; Male; Overweight; Oxidative Stress; Skin; Small Fiber Neuropathy; Sphingolipids

Hydrogen-rich water (HW) has been suggested to possess antioxidant properties of value in treatments of lifestyle diseases and for prevention of latent pathologies. To date, the potential benefits of HW against the deleterious effects of excessive salt intake and hypertension have not been investigated. Here, we first examined the effects of HW or HW supplemented with 0.1% ascorbic acid (HWA) on spontaneously hypertensive rats (SHR) that had been fed a normal diet. In comparison to control rats given distilled water (DW), we found that HW did not significantly influence systolic blood pressure (SBP) or diastolic blood pressure (DBP) in SHR; however, the increase in SBP and DBP were inhibited in the HWA group. Next, four groups of SHR were given DW, 0.1% ascorbic acid-added DW (DWA), HW, or HWA in combination with a 4% NaCl-added diet. SHR fed the 4% NaCl-added diet showed increased hypertension; HWA treatment resulted in a significant reduction in blood pressure. The HWA group tended to have lower plasma angiotensin II levels than the DW group. In addition, urinary volumes and urinary sodium levels were significantly lower in the HWA group than the DW group. Urinary isoprostane, an oxidative stress marker, was also significantly lower in the HWA group, suggesting that the inhibitory effect of HWA on blood pressure elevation was caused by a reduction in oxidative stress. These findings suggest a synergistic interaction between HW and ascorbic acid, and also suggest that HWA ingestion has potential for prevention of hypertension.

Topics: Animals; Ascorbic Acid; Hydrogen; Hypertension; Rats; Rats, Inbred SHR; Sodium Chloride; Water

What is the central question of this study? Does acute intradermal administration of the antioxidant ascorbate augment local forearm cutaneous vasodilatation and sweating via nitric oxide synthase (NOS)-dependent mechanisms during exercise-heat stress in older adults with uncomplicated controlled hypertension? What is the main finding and its importance? Relative to the control site, ascorbate had no effect on forearm cutaneous vascular conductance (CVC) and sweat rate, although CVC was reduced with NOS inhibition in older adults with hypertension. Acute local administration of ascorbate to forearm skin does not modulate heat loss responses during exercise-heat stress in older adults with hypertension.. Nitric oxide synthase (NOS) contributes to the heat loss responses of cutaneous vasodilatation and sweating during exercise. However, the contribution of NOS may be attenuated in individuals with uncomplicated, controlled hypertension due to elevated oxidative stress, which can reduce NO bioavailability. We evaluated the hypothesis that the acute local intradermal administration of the antioxidant ascorbate would enhance cutaneous vasodilatation and sweating via NOS-dependent mechanisms during an exercise-heat stress in adults with hypertension. Habitually active adults who were normotensive (n = 14, 7 females, 62 ± 4 years) or had uncomplicated, controlled hypertension (n = 13, 6 females, 62 ± 5 years) performed 30 min of moderate-intensity (50% of their pre-determined peak oxygen uptake) semi-recumbent cycling in the heat (35°C, 20% relative humidity). Cutaneous vascular conductance (CVC) and sweat rate were assessed at four forearm skin sites continuously perfused with (1) lactated Ringer solution (Control), (2) 10 mM antioxidant ascorbate, (3) 10 mM N

Topics: Aged; Antioxidants; Ascorbic Acid; Female; Heat-Shock Response; Humans; Hypertension; Male; Middle Aged; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Skin; Sweating; Vasodilation

[Figure: see text].

Topics: Acetylcholine; Aged; Ascorbic Acid; Blood Pressure; Endothelium, Vascular; Female; Forearm; Humans; Hypertension; Male; Middle Aged; Regional Blood Flow; Sleep; Sleep Deprivation; Vasodilation; Vasodilator Agents

Exercise and food supplement of vitamin C (VC) are beneficial to human health, especially for those who suffer from hypertension. Here we tend to explore if gut microflora is involved in the anti-hypertensive effects of exercise and VC-supplement therapies.. With the spontaneously hypertensive rat (SHR) model, the small intestine pathology and the fecal microbiota was analyzed along with the pro- and anti-inflammatory cytokines (PICs and AICs) and reactive oxygen species (ROS) in the hypothalamus paraventricular nucleus (PVN) and intestine.. We found that both exercise and VC intake, individually or combined, were able to alleviate the blood pressure in the SHRs comparing to the normotensive control Wistar-kyoto (WKY) rats. The expression level of PICs in the PVN and intestine of the SHRs was down-regulated while the AICs were up-regulated after treatments, together with down-regulation of ROS in the PVN. At meantime, the gut pathology was dramatically improved in the SHRs with exercise training or VC intake. Analysis of the gut microflora revealed significant changes in their composition. Several important micro-organisms that were deficient in the SHRs were found up-regulated by the treatments, including Turicibacter and Romboutsia which are involved in the short-chain fatty acid production.. Exercise training and VC intake individually can modify the gut microflora composition and improve the inflammatory state in both PVN and intestine, which contribute to their anti-hypertensive function. Combination of the two treatments enhanced their effects and worth to be considered as a non-medical aid for the hypertensive patients.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Combined Modality Therapy; Cytokines; Dietary Supplements; Gastrointestinal Microbiome; Hypertension; Oxidative Stress; Physical Conditioning, Animal; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reactive Oxygen Species

Gut dysbiosis and dysregulation of the gut-brain-axis contributes to the pathogenesis of hypertension. Vitamin C (VC) is a common dietary supplement that shows the ability to lower the elevated blood pressure in hypertensive animals. Thus, the hypothesis that the gut microbiota is involved in the anti-hypertensive effect of VC is proposed.. The changes of the gut microbiota and pathology in a spontaneously hypertensive rat (SHR) model after daily oral intake of VC in dosage of 200 or 1000 mg kg. The reduced blood pressure, enriched gut microbiota, improved gut pathology and integrity, and reduced inflammatory responses and oxidative stress in the PVN together suggest that the anti-hypertensive effects of VC involve reshaping of gut microbiota composition and function.

Topics: Administration, Oral; Animals; Antihypertensive Agents; Ascorbic Acid; Blood Pressure; Gastrointestinal Microbiome; Hypertension; Intestines; Oxidative Stress; Paraventricular Hypothalamic Nucleus; Rats, Inbred SHR; Rats, Wistar

Oxidative stress plays an essential role in the vascular tone in hypertension; however, the mechanisms remain unclear.. This study aimed to determine the antioxidant effect of tempol and vitamin C (Vit-C) on the basal tone and vascular remodeling of the aorta in nitric oxide (NO) deficiency-induced hypertensive rats.. Male Sprague-Dawley rats were induced to hypertension by Nω-nitro-L-arginine methyl ester (L-NAME). Animals were randomized as follows: vehicle (Control: CR), CR-tempol, CR-Vit-C, L-NAME, L-NAME-tempol, and L-NAME-Vit-C. After 6 weeks of treatment, the basal aortic tone was evaluated by sodium nitroprusside (SNP) and calcium-free medium. Endothelial function, NO, reduced-to-oxidized glutathione (GSH/GSSG) ratio, resting membrane potential (mP), and vascular remodeling were also measured.. L-NAME rats showed an increased basal tone that was blunted by both SNP (-547 ± 69; n = 7 vs. CR: -7.5 ± 6.7 mg; n = 7; p < 0.001) and calcium-free medium. Tempol or Vit-C did not reverse hypertension, and the high basal tone was decreased only with tempol. In L-NAME rats, only tempol partially improved endothelial function, GSH-to-GSSG ratio, mP values, and vascular remodeling.. Tempol decreased calcium-dependent basal aortic tone and improved vascular homeostasis in L-NAME rats. Vit-C did not lead to a similar effect, suggesting that alterations in the superoxide dismutase pathway may play a role in the basal aortic tone.

Topics: Animals; Antioxidants; Aorta, Thoracic; Ascorbic Acid; Cyclic N-Oxides; Dietary Supplements; Disease Models, Animal; Glutathione; Hypertension; Male; Membrane Potentials; NG-Nitroarginine Methyl Ester; Nitric Oxide; Oxidation-Reduction; Oxidative Stress; Rats, Sprague-Dawley; Spin Labels; Vascular Remodeling; Vasoconstriction

Introduction: resistant arterial hypertension (HAR) is associated with a high risk for cardiovascular events due to oxidative stress. Research has shown the beneficial effects of dietary antioxidants on cardiovascular health. Objective: to analyze and correlate the biochemical, anthropometric profile and intake of antioxidant micronutrients of patients with HAR. Material and methods: the patients underwent a biochemical assessment, and an anthropometric assessment to calculate body mass index (IMC), waist circumference (PCI), hip circumference (PCA), waist-to-hip ratio (ICC), and micronutrient intake assessment: vitamin A, vitamin C, vitamin E, selenium and zinc, estimated by a semi-quantitative food frequency questionnaire and 24-hour recall. The statistical analysis was performed using the SPSS Statistics 20 software. A p-value < 0.05 was considered significant. Results: sixty individuals with HAR were studied, with a mean age of 62.83 ± 10.73 years. Mean IMC was 31.01 ± 5.60 kg/m², PCI, 98.12 ± 15.04 cm, PCA, 110.55 ± 13.16 cm, and ICC, 0.879 ± 0.084. Regarding the biochemical profile, mean total colesterol was 187.65 ± 48.29 mg/dL, triglycerides, 136.38 ± 99.91 mg/dL; HDL-col, 49.00 ± 10.99 mg/dL; LDL-col, 112.01 ± 41.89 mg/dL; glucose, 105.37 ± 14.81 mg/dL, and glycated hemoglobin, 6.29 ± 1.76 %. The average daily intake of antioxidants was: vitamin A, 241.47 ± 191.87 µg/d; vitamin C, 147.02 ± 192.94 mg/d; vitamin E, 1.99 ± 1.82 mg/d; selenium, 36.80 ± 34.56 µg/d, and zinc, 99.91 ± 6.64 mg/d, where 91.38 %, 46.55 %, 93.10 %, 67.24 %, and 46.55 % of the sample were below the recommended intakes, respectively. Conclusion: inadequate antioxidant intake was observed in these patients with HAR, with a high prevalence of obesity, especially visceral adiposity and alterations in lipid profile, conditions that require a greater usage of these micronutrients. We suggest there is a need for dietary planning for these patients to improve their quality of life and their response to antihypertensive treatment.. Introducción: la hipertensión arterial resistente (HAR) se asocia a un alto riesgo de eventos cardiovasculares debido al estrés oxidativo. Los estudios han demostrado los efectos beneficiosos de los antioxidantes dietéticos sobre la salud cardiovascular. Objetivo: analizar y correlacionar el perfil bioquímico y antropométrico, y la ingesta de micronutrientes antioxidantes en pacientes con HAR. Material y métodos: los pacientes se sometieron a una evaluación bioquímica y antropométrica para calcular el índice de masa corporal (IMC), el perímetro de la cintura (PCI), el perímetro de la cadera (PCA), el índice cintura-cadera (ICC) y la ingesta de micronutrientes —vitaminas A, C y E, selenio y zinc— utilizando una encuesta de frecuencia de consumo alimentario y el recordatorio de 24 horas. El análisis estadístico se realizó utilizando el software SPSS Statistics 20, con un valor de p < 0,05 como significativo. Resultados: estudiamos a 60 individuos con HAR de 62,83 ± 10,73 años. El IMC medio fue de 31,01 ± 5,60 kg/m²; el PCI de 98,12 ± 15,04 cm, el PCA de 110,55 ± 13,16 cm y el ICC de 0,879 ± 0,084. Respecto al perfil bioquímico, el colesterol total medio fue de 187,65 ± 48,29 mg/dL, los triglicéridos de 136,38 ± 99,91 mg/dL, el HDL-col de 49,00 ± 10,99 mg/dL, el LDL-col de 112,01 ± 41,89 mg/dL, la glucemia de 105,37 ± 14,81 mg/dL y la hemoglobina glucosilada del 6,29 ± 1,76 %. La ingesta de antioxidantes fue: vitamina A: 241,47 ± 191,87 µg/d; vitamina C: 147,02 ± 192,94 mg/d; vitamina E: 1,99 ± 1,82 mg/d; selenio: 36,80 ± 34,56 µg/d, y zinc: 9,91 ± 6,64 mg/d, y el 91,38 %, 46,55 %, 93,10 %, 67,24 % y 46,55 % de la muestra se encontraron por debajo de lo recomendado, respectivamente. Conclusión: se observó una ingesta insuficiente de antioxidantes en los pacientes con HAR, que presentan una alta prevalencia de obesidad, especialmente de adiposidad visceral y alteraciones del perfil lipídico, afecciones que requieren un mayor uso de estos micronutrientes. Se sugiere la necesidad de una planificación dietética dirigida a estos pacientes para mejorar la calidad de vida y la respuesta al tratamiento antihipertensivo.

Topics: Aged; Anthropometry; Antioxidants; Ascorbic Acid; Blood Glucose; Body Mass Index; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Diet Records; Drug Resistance; Female; Hip; Humans; Hypertension; Male; Micronutrients; Middle Aged; Oxidative Stress; Selenium; Triglycerides; Vitamin A; Vitamin E; Vitamins; Waist Circumference; Waist-Hip Ratio; Zinc

Evidence derived from human clinical studies and experimental animal models shows a causal relationship between adverse pregnancy and increased cardiovascular disease in the adult offspring. However, translational studies isolating mechanisms to design intervention are lacking. Sheep and humans share similar precocial developmental milestones in cardiovascular anatomy and physiology. We tested the hypothesis in sheep that maternal treatment with antioxidants protects against fetal growth restriction and programmed hypertension in adulthood in gestation complicated by chronic fetal hypoxia, the most common adverse consequence in human pregnancy. Using bespoke isobaric chambers, chronically catheterized sheep carrying singletons underwent normoxia or hypoxia (10% oxygen [O2]) ± vitamin C treatment (maternal 200 mg.kg-1 IV daily) for the last third of gestation. In one cohort, the maternal arterial blood gas status, the value at which 50% of the maternal hemoglobin is saturated with oxygen (P50), nitric oxide (NO) bioavailability, oxidative stress, and antioxidant capacity were determined. In another, naturally delivered offspring were raised under normoxia until early adulthood (9 months). Lambs were chronically instrumented and cardiovascular function tested in vivo. Following euthanasia, femoral arterial segments were isolated and endothelial function determined by wire myography. Hypoxic pregnancy induced fetal growth restriction and fetal oxidative stress. At adulthood, it programmed hypertension by enhancing vasoconstrictor reactivity and impairing NO-independent endothelial function. Maternal vitamin C in hypoxic pregnancy improved transplacental oxygenation and enhanced fetal antioxidant capacity while increasing NO bioavailability, offsetting constrictor hyper-reactivity and replenishing endothelial function in the adult offspring. These discoveries provide novel insight into mechanisms and interventions against fetal growth restriction and adult-onset programmed hypertension in an animal model of complicated pregnancy in a species of similar temporal developmental milestones to humans.

Topics: Animals; Antioxidants; Ascorbic Acid; Female; Fetal Growth Retardation; Fetal Hypoxia; Hypertension; Hypoxia; Nitric Oxide; Oxidative Stress; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Sheep

The present research work highlights the development of multicomponent solid form of the antihypertensive drug irbesartan (IRB) to improve its biopharmaceutical attributes. Mechanochemical synthesis of a new solid form of IRB with coformers having antioxidant properties (syringic acid, nicotinic acid, and ascorbic acid) resulted into three eutectic mixtures (EMs). Formation of eutectic was ascertained by differential scanning calorimetry whereas exact stoichiometry (50/50% w/w) was established by phase diagram and Tamman's triangle. The strong homomeric interaction between individual components and steric hindrances is responsible for the eutectic formation. EMs exhibited superior apparent solubility (five- to nine fold) and significant enhancement in intrinsic dissolution rate (two- to three fold) as compared to the plain drug. In vivo pharmacokinetic and in vivo pharmacodynamic studies revealed a significant improvement in the biopharmaceutical performance of EMs. Marked protection against oxidative stress was observed in EMs over plain drug by controlling the level/activity of plasma H

Topics: Animals; Antihypertensive Agents; Antioxidants; Ascorbic Acid; Biphenyl Compounds; Calorimetry, Differential Scanning; Gallic Acid; Hydrogen Peroxide; Hypertension; Irbesartan; Kidney; Male; Niacin; Rats; Solubility; Tetrazoles

Nitrite reduces blood pressure (BP) in both clinical and experimental hypertension. This effect is attributable to the formation of nitric oxide (NO) and other NO-related species, which may be improved by ascorbate or other antioxidants. However, the BP responses to oral nitrite result, at least in part, of increased gastric S-nitrosothiol formation. This study tested the hypothesis that ascorbate may destroy S-nitrosothiols and therefore not all doses of ascorbate enhance the BP responses to oral nitrite. We assessed the BP responses to oral sodim nitrite (0.2 mmol/kg) in L-NAME hypertensive rats pretreated with ascorbate (0, 0.02, 0.2, or 2 mmol/kg). Plasma and gastric wall concentrations of nitrite and nitroso compounds concentrations were determined using an ozone-based reductive chemiluminescence assay. Nitrate concentrations were determined using the Griess reaction. Free thiol concentrations were determined by a colorimetric assay. The BP responses to nitrite exhibited a bell-shape profile as they were not modified by ascorbate 0.02 mmol/l, whereas the 0.2 mmol/kg dose enhanced and the 2 mmol/kg dose attenuated BP responses. In parallel with BP responses, nitrite-induced increases in plasma nitrite and RSNO species were not modified by ascorbate 0.02 mmol/l, whereas the 0.2 mmol/kg dose enhanced and the 2 mmol/kg dose attenuated them. Similar experiments were carried out with an equimolar dose of S-nitrosogluthathione. Ascorbate dose-dependently impaired the BP responses to S-nitrosogluthathione, and the corresponding increases in plasma RSNO, but not in plasma nitrite concentrations. This is the first study to show that while ascorbate dose-dependently impairs the BP responses to oral S-nitrosogluthathione, there are contrasting effects when low versus high ascorbate doses are compared with respect to its effects on the blood pressure responses to oral nitrite administration. Our findings may have special implications to patients taking ascorbate, as high doses of this vitamin may impair protective mechanisms associated with nitrite or nitrate from dietary sources.

Topics: Administration, Oral; Animals; Ascorbic Acid; Blood Pressure; Hypertension; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Nitrites; Rats; Rats, Wistar

A family of 12 members of Naphthalene-2-ol-indolin-2-one-thiocarbamides (5a-l) with pharmacological potentials of cardiovascular modulator were efficiently synthesized and evaluated. These compounds show inhibitory activity on angiotensin-converting enzyme (ACE), which is a principal constituent of the renin-angiotensin system and causative source for hypertension (HTN) (elevated blood pressure) and congestive heart failure (CHF), a parameter that was tested in this report. Prior to this, to get more insight into the binding mode and inhibition of human ACE C-domain (PDB ID: 2XY9) and N-domain (PDB ID: 3NXQ) compounds 5a-l was docked into the active site of them. The established inhibitory constant (Ki) (range 40-500 nM) and least binding affinities (-18.52 to -30.57 kcal/mol) indicated the therapeutic selectivity of compounds 5a-l towards ACE C-domain inhibition over ACE N-domain. The cytotoxicity effect of most potent compounds among 5a-l were tested in normal breast cells and MCF-7 cell lines. Simultaneously, H

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Heart Failure; Humans; Hypertension; Indoles; Models, Molecular; Molecular Structure; Structure-Activity Relationship; Thrombolytic Therapy

The objective of the present work was to evaluate the toxic effects of cobalt chloride, a potent oxidative stress-inducing chemical, at 650 ppm in rats and the protective effect of quercetin and/or vitamin C against the cobalt chloride-induced toxicity. Thirty rats were randomly selected, and assigned to one of five groups: control, cobalt chloride, cobalt chloride + quercetin, cobalt chloride + vitamin C and cobalt chloride + quercetin + vitamin C. The exposure of rats to cobalt chloride led to a significant increase (p < 0.05) in malondialdehyde (MDA) and hydrogen peroxide (H

Topics: Animals; Ascorbic Acid; Cobalt; Gene Expression Regulation; Hypertension; Male; NF-kappa B; Oxidative Stress; Quercetin; Rats; Rats, Wistar

The worldwide incidence of diabetes has increased dramatically along with widespread lifestyle and dietary changes. Diets high in fat are strongly associated with the development of obesity and can induce insulin resistance in humans and animals. It is clear that obesity constitutes a risk factor for contributing to the development of type 2 diabetes. In the present study, we investigated the therapeutic potential action of vanillic acid on diabetes associated complications using a rat model. Rats were made diabetic hypertensive by high fat diet (HFD) for 20 weeks and were treated with vanillic acid (50mg/kg bw) for last 8 weeks. The effects of vanillic acid on glucose, plasma insulin, systolic and diastolic blood pressure, thiobarbituric acid reactive substances (TBARS), hydroperoxides as a lipid peroxidation marker, and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin C and vitamin E as an antioxidant marker, AST and ALT as a liver function marker, urea, uric acid and creatinine as a kidney function marker were investigated. Histopathology of liver and kidney was also investigated as part of the pathology of diabetes. Treatment of diabetic rats with oral administration of vanillic acid at a dose of 50mgkg/body weight for 8 weeks resulted in a significant decrease in fasting plasma glucose, insulin and blood pressure levels in comparison with diabetic control group. The antioxidant activities were significantly increased and the levels of lipid peroxidation markers were significantly decreased in diabetic hypertensive rats treated with vanillic acid. These results suggest that vanillic acid offer a modulatory effect on control of diabetic hypertension by reduction of blood glucose, insulin and blood pressure, combating oxidative stress by activation of tissue antioxidants.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Glucose; Blood Pressure; Catalase; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Glutathione; Glutathione Peroxidase; Hypertension; Insulin; Lipid Peroxidation; Male; Rats; Rats, Wistar; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vanillic Acid; Vitamin E

Background Phenylhydrazine (PHE) in experimental animal models has been widely reported to cause haemolytic anaemia, via the induction of oxidative stress and thus causing deleterious cardiovascular complications. Hence, this study was designed to evaluate the possible modulatory role of melatonin (MLT) or vitamin C when co-administered with PHE. Methods Anaemia was established with PHE administration. MLT or vitamin C was co-administered with PHE. Haematological parameters, markers of oxidative stress, enzymic and non-enzymic antioxidants, blood pressure and electrocardiograms were assessed. Results PHE administration led to a significant (p<0.05) increase in malondialdehyde (MDA), and hydrogen peroxide (H2O2) generated in cardiac, renal and red blood cell (RBC) lysates. PHE also significantly reduced the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD) and reduced glutathione (GSH) contents, respectively. The RBC counts, haemoglobin (Hb) concentration and packed cell volume (PCV) were also significantly reduced following the administration of PHE. Furthermore, the systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MABP) increased significantly in rats administered PHE alone. Similarly, PHE administration led to a significant drop in heart rate but prolonged QRS, QT and QTc interval. Pathology of the heart and kidney was also observed in PHE treated group. However, treatment with MLT and vitamin C improved enzymic and non-enzymic antioxidant system together with the restoration of SBP, DBP and MABP to near normal. The architectural anarchy observed in the heart and kidney of PHE administered rats was reversed to some extent. Conclusions Hence, MLT and vitamin C could be employed as therapeutic targets in various cardiovascular diseases and its complications.

Topics: Anemia, Hemolytic; Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Catalase; Erythrocytes; Glutathione; Glutathione Peroxidase; Heart; Hemoglobins; Hydrogen Peroxide; Hypertension; Kidney; Male; Malondialdehyde; Melatonin; Myocardium; Oxidative Stress; Phenylhydrazines; Rats, Wistar; Superoxide Dismutase; Vitamins

Regular intake of vitamin C/ascorbate reduces blood pressure (BP) in hypertensives. High-dose intravenous vitamin C (IVC) achieves higher plasma levels; however, there is a paucity of research on acute BP effects. Our study is the first to investigate the effect of high-dose IVC, with or without concomitant i.v. nutrients, on BP during i.v.. A cohort of adult patients scheduled to receive IVC treatment for infection, cancer or fatigue, as prescribed by their treating doctor, participated at a Melbourne clinic, Australia. Ambulatory BP was assessed every 10 min over 90 min during i.v.. Patients received 15-100 g of IVC alone or in addition to i.v. vitamin B, glutathione, magnesium or zinc. BP change over time adjusted for baseline BP, IVC dosage, i.v. treatment and BMI was analysed.. A total of 77 mostly normotensive patients participated, with a third receiving IVC alone (42±20 g), and two-thirds also received other i.v. nutrients. IVC alone (>30 g) reduced the mean BP up to 8-9 mmHg in prehypertensive patients. In contrast, concomitant intravenous vitamin B12 (IVB12) significantly increased the mean BP by 11-13 mmHg. Comparison of BP change during IVC versus IVC+IVB12 indicated a highly significant difference [systolic blood pressure: mean difference (SD)=16.6 (17.8) mmHg, P<0.001; diastolic blood pressure: mean difference (SD)=12.5 (16.7) mmHg, P=0.003].. Our study suggests an acute BP-reducing effect of high-dose IVC, particularly with dosages above 30 g, and in patients with prehypertension and normal BMI. Furthermore, our study indicated a marked and clinically relevant hypertensive effect of IVB12, suggesting routine BP monitoring during i.v. therapy in clinical practice.

Topics: Administration, Intravenous; Adult; Aged; Ascorbic Acid; Blood Pressure; Female; Glutathione; Humans; Hypertension; Magnesium; Male; Middle Aged; Vitamin B 12; Zinc

Oxidative stress plays a key role in the patho-physiology of hypertension. (-)-Epicatechin has many important biological properties.. The present study was undertaken to evaluate effect of (-)-epicatechin on protein carbonyl content in gender-based hypertensive patients and normal subjects.. The study was carried out on 83 normal (male: 42; female: 41) and 62 hypertensive subjects (male: 32; female: 30). In vitro effect on (-)-epicatechin and L-ascorbic acid was estimated on protein carbonyl content.. Result showed a significant (p < 0.001) increase in protein carbonyl content in hypertensive patients but no gender-based difference was observed. (-)-epicatechin shows significant (p < 0.001) dose-dependent effect as compared to L-ascorbic acid, which is manifested as decrease in protein carbonyl content.. We hypothesizes that a higher intake of (-)-epicatechin may provide protection against hypertension in males and females.

Topics: Antioxidants; Ascorbic Acid; Case-Control Studies; Catechin; Erythrocytes; Female; Humans; Hypertension; In Vitro Techniques; Male; Middle Aged; Oxidative Stress; Protein Carbonylation; Proteins

Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Prenatal exposure to lipopolysaccharide (LPS) leads to hypertension in a rat offspring. However, the mechanism is still unclear. This study unraveled epigenetic mechanism for this and explored the protective effects of ascorbic acid against hypertension on prenatal inflammation-induced offspring. Prenatal LPS exposure resulted in an increase of intrarenal oxidative stress and enhanced angiotensin-converting enzyme 1 (ACE1) gene expression at the mRNA and protein levels in 6- and 12-week-old offspring, correlating with the augmentation of histone H3 acetylation (H3AC) on the ACE1 promoter. However, the prenatal ascorbic acid treatment decreased the LPS-induced expression of ACE1, protected against intrarenal oxidative stress, and reversed the altered histone modification on the ACE1 promoter, showing the protective effect in offspring of prenatal LPS stimulation. Our study demonstrates that ascorbic acid is able to prevent hypertension in offspring from prenatal inflammation exposure. Thus, ascorbic acid can be a new approach towards the prevention of fetal programming hypertension.

Topics: Acetylation; Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Body Weight; CpG Islands; Epigenesis, Genetic; Female; Gene Expression Regulation, Developmental; Histones; Hypertension; Inflammation; Kidney; Lipopolysaccharides; Oxidative Stress; Peptidyl-Dipeptidase A; Pregnancy; Prenatal Exposure Delayed Effects; Promoter Regions, Genetic; Rats; Rats, Sprague-Dawley; Risk Factors; RNA, Messenger

We assessed whether acute intra-arterial infusion of exogenous ghrelin can improve endothelial dysfunction by restoring nitric oxide (NO) availability in the forearm microcirculation of essential hypertensive patients. The effect of ghrelin on endothelial dysfunction (pressurized myograph), vascular oxidative stress generation (fluorescent dihydroethidium), and phosphorylation of p47phox (western blot), an index of NAD(P)H oxidase activation, in isolated small arteries taken from essential hypertensive patients (subcutaneous biopsy) were also investigated.. In 18 normotensive control subjects and 18 essential hypertensive patients, we studied the forearm blood flow (strain-gauge plethysmography) response to intra-arterial acetylcholine, repeated under NO synthase inhibitor N(G)-monomethyl-l-arginine (l-NMMA) or the antioxidant ascorbic acid. The protocol was repeated at the end of exogenous ghrelin intra-arterial infusion. In hypertensive patients, ghrelin normalized the blunted response to acetylcholine, restored the inhibiting effect of l-NMMA and abrogated the potentiating effect of ascorbic acid on acetylcholine. In controls, ghrelin failed to modify these vascular responses. In hypertensive patients, ghrelin decreased venous levels of malondialdehyde, lipoperoxide, and interleukin-6, and concomitantly increased endogenous antioxidant capacity. Small vessels from hypertensive patients showed an enhanced intravascular oxidative stress, which was strongly and similarly decreased by incubation with ghrelin, the NAD(P)H oxidase inhibitor gp91 ds-tat, or both. Ghrelin also normalized the overexpression of p47 phosphorylation and restored the NO availability in small vessels from hypertensive patients.. Exogenous ghrelin increases endothelial dysfunction by restoring NO availability in the forearm microcirculation of essential hypertensive patients, an effect ascribable to an antioxidant effect via inhibition of NAD(P)H oxidase activation.

Topics: Analysis of Variance; Antioxidants; Ascorbic Acid; Case-Control Studies; Endothelium, Vascular; Enzyme Inhibitors; Female; Forearm; Ghrelin; Humans; Hypertension; Infusions, Intra-Arterial; Male; Middle Aged; NADPH Oxidases; Nitric Oxide; omega-N-Methylarginine; Oxidative Stress; Reactive Oxygen Species; Superoxides; Vasodilator Agents

In our previous studies, veratric acid (VA) shows beneficial effect on hypertension and its associated dyslipidaemia. In continuation, this study was designed to investigate the effect of VA, one of the major benzoic acid derivatives from vegetables and fruits, on cardiovascular remodelling in hypertensive rats, primarily assessed by functional studies using Langendorff isolated heart system and organ bath system. Hypertension was induced in male albino Wistar rats by oral administration of N ω -nitro-l-arginine methyl ester hydrochloride (l-NAME) (40 mg/kg body weight (b.w.)) in drinking water for 4 weeks. VA was orally administered at a dose of 40 mg/kg b.w. l-NAME-treated rats showed impaired cardiac ventricular and vascular function, evaluated by Langendorff isolated heart system and organ bath studies, respectively; a significant increase in the lipid peroxidation products such as thiobarbituric acid-reactive substances and lipid hydroperoxides in aorta; and a significant decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase and levels of GSH, vitamin C and vitamin E in aorta. Fibrotic remodelling of the aorta and heart were assessed by Masson's Trichrome staining and Van Gieson's staining, respectively. In addition, l-NAME rats showed increased heart fibronectin expression assessed by immunohistochemical analysis. VA supplementation throughout the experimental period significantly normalised cardiovascular function, oxidative stress, antioxidant status and fibrotic remodelling of tissues. These results of the present study conclude that VA acts as a protective agent against hypertension-associated cardiovascular remodelling.

Topics: Administration, Oral; Animals; Antioxidants; Aorta; Ascorbic Acid; Cardiovascular Diseases; Cardiovascular System; Catalase; Disease Models, Animal; Dose-Response Relationship, Drug; Fruit; Glutathione; Glutathione Peroxidase; Hypertension; Lipid Peroxidation; Lipid Peroxides; Male; NG-Nitroarginine Methyl Ester; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vanillic Acid; Vascular Remodeling; Vegetables; Vitamin E

The occurrence of hyperglycemia in non-diabetics during development of acute coronary ischemia (ACI) indicates latent glucose metabolism disorder, or is a case of newly discovered diabetes mellitus (DM) as a result of stress. Acute coronary syndrome refers to a group of clinical syndromes caused by a sudden circulatory disorder in coronary arteries, resulting in the corresponding myocardial ischemia. It covers range from unstable angina and myocardial infarction (MI) without Q wave in the electrocardiogram finding (NSTEMI) up to myocardial infarction with Q wave in the electrocardiogram finding (STEMI).. To determine the incidence of hyperglycemia in non-diabetics immediately after the occurrence of acute coronary ischemia and assess its risk factors.. The sample included 80 respondents. Men dominated with a total prevalence of 77.5%. The respondent was at mean age of 62.8±13.8 years. During the first measurement, immediately after hospital admission, 50% of respondents had increased blood glucose value and during the second measurement 62%. Hypertension as a risk factor has 54% and 56% smoking. The incidence of stress diabetes after ACI does not depend on the diagnosis of hypertension, χ(2)=0.050; p=0.823. The differences of mean values (median) BMI between examined persons with/without stress DM are not statistically significant p=0.402. Independent t-test showed that there was no statistically significant difference in the average values of HDL and LDL in patients with stress diabetes than in patients without diabetes stress after ACI p>0.05. For each year of age odds ratio for "stress diabetes" increases by 7% and 95% CI is 2% -12%.. The incidence of stress diabetes ACI is not dependent on the working diagnosis (MI or angina pectoris). As risk factors we set hypertension and current smoking. There were no statistically significant associations between active smoking and hypertension as a risk factor in relation to occurrence of stress diabetes.

Topics: Acute Disease; Age Factors; Ascorbic Acid; Cholecalciferol; Dehydroepiandrosterone; Female; Humans; Hypertension; Hypoglycemia; Male; Middle Aged; Myocardial Ischemia; Nicotinic Acids; Plant Extracts; Risk Factors; Sex Factors

Vitamin C may reduce risk of hypertension, either in itself or by marking a healthy diet pattern. We assessed whether plasma ascorbic acid and the a priori diet quality score relate to incident hypertension and whether they explain each other's predictive abilities. Data were from 2884 black and white adults (43% black, mean age 35 years) initially hypertension-free in the Coronary Artery Risk Development in Young Adults Study (study year 10, 1995-1996). Plasma ascorbic acid was assessed at year 10 and the diet quality score at year 7. Eight-hundred-and-forty cases of hypertension were documented between years 10 and 25. After multiple adjustments, each 12-point (1 SD) higher diet quality score at year 7 related to mean 3.7 μmol/L (95% CI 2.9 to 4.6) higher plasma ascorbic acid at year 10. In separate multiple-adjusted Cox regression models, the hazard ratio of hypertension per 19.6-μmol/L (1 SD) higher ascorbic acid was 0.85 (95% CI 0.79-0.92) and per 12-points higher diet score 0.86 (95% CI 0.79-0.94). These hazard ratios changed little with mutual adjustment of ascorbic acid and diet quality score for each other, or when adjusted for anthropometric variables, diabetes, and systolic blood pressure at year 10. Intake of dietary vitamin C and several food groups high in vitamin C content were inversely related to hypertension, whereas supplemental vitamin C was not. In conclusion, plasma ascorbic acid and the a priori diet quality score independently predict hypertension. This suggests that hypertension risk is reduced by improving overall diet quality and/or vitamin C status. The inverse association seen for dietary but not for supplemental vitamin C suggests that vitamin C status is preferably improved by eating foods rich in vitamin C, in addition to not smoking and other dietary habits that prevent ascorbic acid from depletion.

Topics: Adult; Ascorbic Acid; Black People; Blood Pressure; Diet; Humans; Hypertension; Incidental Findings; Prospective Studies; Regression Analysis; Vitamins; White People; Young Adult

Various species of the genus Passiflora have been extensively used in traditional medicine as sedatives, anxiolytics, diuretics and analgesics. In the present study, after the identification and quantification of phytochemical compounds from yellow passion fruit pulp by liquid chromatography-photodiode array-mass spectrometry (HPLC-PDA-MS/MS), its antihypertensive effect was investigated on spontaneously hypertensive rats. Additionally, the renal function, evaluated by kidney/body weight, serum creatinine, proteinuria, urinary flow, reduced glutathione (GSH) levels and thiobarbituric acid-reactive substances (TBARS) and mutagenicity in bone marrow cells were assessed to evaluate the safety of passion fruit consumption. Yellow passion fruit pulp (5, 6 or 8 g/kg b.w.) was administered by gavage once a day for 5 consecutive days. HLPC-PDA-MS/MS analysis revealed that yellow passion fruit pulp contains phenolic compounds, ascorbic acid, carotenoids and flavonoids. The highest dose of passion fruit pulp significantly reduced the systolic blood pressure, increased the GSH levels and decreased TBARS. There were no changes in renal function parameters or the frequency of micronuclei in bone marrow cells. In conclusion, the antihypertensive effect of yellow passion fruit pulp, at least in part, might be due to the enhancement of the antioxidant status. The exact mechanisms responsible by this effect need further investigation.

Topics: Animals; Antihypertensive Agents; Antioxidants; Ascorbic Acid; Blood Pressure; Bone Marrow; Carotenoids; Chromatography, High Pressure Liquid; Creatinine; Flavonoids; Fruit; Glutathione; Hypertension; Kidney; Male; Oxidative Stress; Passiflora; Phenols; Rats; Rats, Inbred SHR; Rats, Wistar; Tandem Mass Spectrometry; Thiobarbituric Acid Reactive Substances

This study aimed to investigate the influence of acute glycemic load on vascular endothelial function in patients with hypertension and to evaluate the protective effect of vitamins C and E during the acute glycemic phase. We randomly selected 39 hypertensive patients and 21 normal subjects and divided them into 3 groups: 75 g oral glucose (glycemic load group), 75 g glucose+0.9 g vitamin C (VC group), 75 g glucose+2 g vitamin C+0.8 g vitamin E (VC+VE group). Extravascular color Doppler ultrasound was used to detect brachial artery flow-mediated vasodilation at 0, 1, 2, and 3 h, and, at the same time, serum anti-oxidant products were measured. Basic endothelial functions in patients with hypertension were decreased in the glycemic load group (9.48±3.33 versus 13.09±6.78%, P<0.05), and was even more depressed in the hypertensive group (9.48±3.33 versus 14.20±6.48%, P<0.05). Antioxidant vitamins played a dose-dependent protective role on acute damage of endothelial function due to glycemic load. Acute high blood sugar damaged vascular endothelial functions, especially in hypertensive patients, but this effect can be reversed by large doses of vitamin C and E.

Topics: Adult; Antioxidants; Ascorbic Acid; Blood Glucose; Cohort Studies; Endothelium, Vascular; Essential Hypertension; Female; Glucose; Humans; Hypertension; Male; Middle Aged; Risk Factors; Superoxide Dismutase; Superoxides; Vasodilation; Vitamin E

The present study was undertaken to investigate the antihypertensive and antioxidant effects of sesamol on uninephrectomized deoxycorticosterone acetate (DOCA)-salt-induced hypertensive rats. Hypertension was induced in surgically single-kidney-removed (left) adult male albino Wistar rats, weighing 180-200 g, by injecting DOCA (25 mg/kg BW) subcutaneously twice a week for 6 weeks, with saline instead of tap water for drinking. Rats were treated with three different doses of sesamol (50, 100 and 200 mg/kg BW) post-orally by gavage daily for 6 weeks. Hypertension was revealed by increased systolic and diastolic blood pressure and the toxicity of DOCA-salt was determined using hepatic marker enzymes, aspartate aminotransferase, alanine aminotransferase, alkaline phospatase and gamma-glutamyl transpeptidase; and, lipid peroxidative markers, thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes were assayed. The activities of enzymatic antioxidants, superoxide dismutase, catalase and glutathione peroxidase and the levels of non-enzymatic antioxidants (vitamin C, vitamin E and reduced glutathione) were evaluated in erythrocytes, plasma and tissues. Post-oral administration of sesamol at the dosage of 50 mg/kg BW remarkably decreased systolic and diastolic blood pressure, hepatic marker enzyme activities and lipid peroxidation products and also enhanced the antioxidant activity. The biochemical observations were also supported by histopathological examinations of the rat liver, kidney and heart sections. These results suggest that sesamol possesses antihypertensive and antioxidant effects.

Topics: Animals; Antihypertensive Agents; Ascorbic Acid; Benzodioxoles; Blood Pressure; Catalase; Desoxycorticosterone Acetate; Drug Evaluation, Preclinical; Erythrocytes; Glutathione; Glutathione Peroxidase; Heart; Hypertension; Kidney; Lipid Peroxidation; Liver; Male; Myocardium; Nephrectomy; Oxidative Stress; Phenols; Rats; Rats, Wistar; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin E

Senescence marker protein 30 (SMP30) is assumed to behave as an anti-aging factor. Recently, we have demonstrated that deficiency of SMP30 exacerbates angiotensin II-induced cardiac hypertrophy, dysfunction and remodeling, suggesting that SMP30 may have a protective role in the heart. Thus, this study aimed to test the hypothesis that up-regulation of SMP30 inhibits cardiac adverse remodeling in response to angiotensin II.. We generated transgenic mice with cardiac-specific overexpression of SMP30 gene using α-myosin heavy chain promoter. Transgenic mice and wild-type littermate mice were subjected to continuous angiotensin II infusion (800 ng/kg/min).. After 14 days, heart weight and left ventricular weight were lower in transgenic mice than in wild-type mice, although blood pressure was similarly elevated during angiotensin II infusion. Cardiac hypertrophy and diastolic dysfunction in response to angiotensin II were prevented in transgenic mice compared with wild-type mice. The degree of cardiac fibrosis by angiotensin II was lower in transgenic mice than in wild-type mice. Angiotensin II-induced generation of superoxide and subsequent cellular senescence were attenuated in transgenic mouse hearts compared with wild-type mice.. Cardiac-specific overexpression of SMP30 inhibited angiotensin II-induced cardiac adverse remodeling. SMP30 has a cardio-protective role with anti-oxidative and anti-aging effects and could be a novel therapeutic target to prevent cardiac hypertrophy and remodeling due to hypertension.

Topics: Angiotensin II; Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Calcium-Binding Proteins; Cardiomegaly; Cellular Senescence; Diastole; Echocardiography; Fibrosis; Hypertension; Intracellular Signaling Peptides and Proteins; Male; Mice; Mice, Transgenic; Oxidative Stress; Promoter Regions, Genetic; Superoxides

The present study investigated the effects of a 6-week swimming training on blood pressure, nitric oxide (NO) levels and oxidative stress parameters such as protein and lipid oxidation, antioxidant enzyme activity and endogenous non-enzymatic antioxidant content in kidney and circulating fluids, as well as on serum biochemical parameters (cholesterol, triglycerides, urea and creatinine) from Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertension treated rats. Animals were divided into four groups (n = 10): Control, Exercise, L-NAME and Exercise L-NAME. Results showed that exercise prevented a decrease in NO levels in hypertensive rats (P < 0·05). An increase in protein and lipid oxidation observed in the L-NAME-treated group was reverted by physical training in serum from the Exercise L-NAME group (P < 0·05). A decrease in the catalase (CAT) and superoxide dismutase (SOD) activities in the L-NAME group was observed when compared with normotensive groups (P < 0·05). In kidney, exercise significantly augmented the CAT and SOD activities in the Exercise L-NAME group when compared with the L-NAME group (P < 0·05). There was a decrease in the non-protein thiols (NPSH) levels in the L-NAME-treated group when compared with the normotensive groups (P < 0·05). In the Exercise L-NAME group, there was an increase in NPSH levels when compared with the L-NAME group (P < 0·05). The elevation in serum cholesterol, triglycerides, urea and creatinine levels observed in the L-NAME group were reverted to levels close to normal by exercise in the Exercise L-NAME group (P < 0·05). Exercise training had hypotensive effect, reducing blood pressure in the Exercise L-NAME group (P < 0·05). These findings suggest that physical training could have a protector effect against oxidative damage and renal injury caused by hypertension.

Topics: Animals; Ascorbic Acid; Biomarkers; Blood Pressure; Body Weight; Catalase; Heart Rate; Hypertension; Kidney; Lipid Peroxidation; Lipids; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Oxidation-Reduction; Oxidative Stress; Physical Conditioning, Animal; Protein Carbonylation; Rats; Rats, Wistar; Sulfhydryl Compounds; Superoxide Dismutase; Swimming; Systole; Thiobarbituric Acid Reactive Substances

Essential hypertension, as well as other established cardiovascular risk factors, is associated with endothelial dysfunction. Hypertensive patients with a nondipper circadian pattern have a greater risk of cerebrovascular and cardiovascular complications in comparison with those with a dipper circadian pattern. In this study, we evaluated the association between nondipper pattern and endothelial function in patients with essential hypertension.. We evaluated the forearm blood flow (FBF) response to intraarterial acetylcholine (ACh), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator, infusions in 190 hypertensive patients stratified according to dipper and nondipper status. The FBF was measured by strain-gauge plethysmography. Effects of oxidative stress on FBF were evaluated by intraarterial infusion of vitamin C. Ambulatory BP monitorings were obtained by a validated oscillometric device (SpaceLabs 90207 Monitor Inc., Issaquah, WA, USA).. Systolic and diastolic blood pressures were higher during daytime and lower during night-time in dipper subjects than in nondippers. The peak percent increase in ACh-stimulated FBF was higher in dippers than in nondippers (473% vs. 228%, P < 0.001). The FBF responses to SNP were similar in dipper and nondipper patients. The FBF response to ACh during coinfusion of vitamin C was higher in nondippers rather than in dipper hypertensives.. Present data demonstrate that endothelium-dependent vasodilation is impaired in patients who have nondipper hypertension. The effects of vitamin C on impaired ACh-stimulated vasodilation support the hypothesis that oxidative stress contributes to endothelial dysfunction of nondipper hypertensive patients.

Topics: Acetylcholine; Adult; Aged; Analysis of Variance; Antioxidants; Ascorbic Acid; Blood Pressure; Circadian Rhythm; Endothelium, Vascular; Female; Forearm; Humans; Hypertension; Injections, Intravenous; Male; Middle Aged; Nitroprusside; Oxidative Stress; Plethysmography; Regional Blood Flow; Vasodilator Agents; Young Adult

The present study was aimed to evaluate the antihypertensive effect of diosmin in deoxycorticosterone acetate (DOCA)-salt induced hypertension in male Wistar rats. Hypertension was induced in uninephrectomized rats by weekly twice subcutaneous injection of DOCA (25 mg/kg body weight) and 1% NaCl in the drinking water for six consecutive weeks. The important pathological events that occurred in DOCA-salt treated rats were significant increase in systolic, diastolic blood pressure, sodium and chloride in serum and lipid peroxidation products (thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes) in plasma and tissues (liver, kidney, heart and aorta) and significant decrease in serum potassium, total nitrite and nitrate levels in plasma. The activities of hepatic aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase and the levels of renal urea, uric acid, creatinine in serum, water intake, and organ weight (kidney and heart) were significantly increased in DOCA-salt hypertensive rats. DOCA-salt treated rats also showed a significant decrease in body weight, activities of superoxide dismutase, catalase and glutathione peroxidase in erythrocyte and tissues and the levels of reduced glutathione, vitamin C and vitamin E in plasma and tissues. Treatment with diosmin (25, 50 and 100 mg/kg body weight) brings back all the above parameters to near normal level, in which 50 mg/kg body weight showed the highest effect than that of other two doses. Histopathology of heart and kidney also confirmed the protective effect of diosmin. Thus the experiment clearly showed that diosmin acts as an antihypertensive agent against DOCA-salt induced hypertension.

Topics: Animals; Antihypertensive Agents; Aorta; Ascorbic Acid; Blood Pressure; Body Weight; Desoxycorticosterone; Diosmin; Disease Models, Animal; Flavonoids; Glutathione; Heart; Hypertension; Kidney; Lipid Peroxides; Liver; Male; Myocardium; Nitrates; Nitrites; Oxidoreductases; Potassium; Rats; Rats, Wistar; Sodium Chloride; Vitamin E

Although the antioxidant properties of flavonoids are well documented, it is still unclear whether these effects are dependent on radical scavenging or iron chelating activities. Oxidative stress, a state of excessive reactive oxygen species (ROS) activity, is associated with vascular disease conditions such as hypertension. Both the anti- and pro-oxidant effects of tea catechins have been implicated in the alterations of cellular functions that determine their chemoprotective and therapeutic potentials in health and diseases. The present study examined the concentration dependent (10(-7) to 10(-4)  m) effects of (-)-epicatechin and L-ascorbic acid on Na(+) /K(+) -ATPase and Ca(2+) -ATPase activity in hypertensive patients and normal subjects. L-ascorbic acid has been used as a positive control to compare the effect of (-)-epicatechin. A significant (p < 0.0001) decrease in the activities of Na(+) /K(+) -ATPase and Ca(2+) -ATPase was observed in hypertensive patients compared with normal subjects. We report that (-)-epicatechin shows a significant (p < 0.001) dose-dependent protective effect against oxidative stress induced by tert-butyl hydroperoxide (t-BHP), which is manisfested as a decrease in the activity of erythrocyte Na(+) /K(+) -ATPase and Ca(2+) -ATPase, in hypertensive patients as well as normal subjects. The effect of L-ascorbic acid was also significant (p < 0.001) and was comparable with that of (-)-epicatechin.

Topics: Ascorbic Acid; Calcium-Transporting ATPases; Case-Control Studies; Catechin; Enzyme Inhibitors; Humans; Hypertension; Middle Aged; Oxidative Stress; Sodium-Potassium-Exchanging ATPase; tert-Butylhydroperoxide

Essential hypertension is characterized by both increased oxidative stress and sympathetic traffic. Experimental studies have shown that reactive oxygen species can modulate autonomic activity.. The aim of this study was to determine whether acute administration of the antioxidant vitamin C modifies sympathetic nerve activity in essential hypertension.. Thirty-two untreated patients with essential hypertension and 20 normotensive subjects received vitamin C (3 g intravenously in 5 min) or vehicle. Heart rate, noninvasive beat-to-beat blood pressure, and muscle sympathetic nerve activity (microneurography) were monitored at baseline and up to 20 min after the infusion. Spectral analysis of RR interval variability and spontaneous baroreflex sensitivity were also computed.. Vitamin C infusion significantly lowered blood pressure in hypertensive patients but not in normotensive subjects (maximal changes in systolic blood pressure: -4.9 ± 10.1 compared with -0.7 ± 4.0 mm Hg, respectively; P < 0.05). Moreover, muscle sympathetic nerve activity was significantly reduced after vitamin C infusion in hypertensive patients (from 53.3 ± 12.2 to 47.4 ± 11.5 bursts/100 heart beats; P < 0.01) but not in healthy subjects (from 42.0 ± 10.1 to 42.7 ± 11.8 bursts/100 heart beats; NS). On the contrary, in 16 hypertensive patients, sodium nitroprusside in equidepressor doses induced a significant increase in muscle sympathetic nerve activity compared with vitamin C (+10.0 ± 6.9 bursts/100 heart beats). Sympathovagal balance and spontaneous baroreflex sensitivity were restored during vitamin C infusion in hypertensive subjects.. These results indicate that acute administration of vitamin C is able to reduce cardiovascular adrenergic drive in hypertensive patients, which suggests that oxidative stress is involved in the regulation of sympathetic activity in essential hypertension.

Topics: Adult; Ascorbic Acid; Baroreflex; Blood Pressure; Case-Control Studies; Female; Heart; Heart Rate; Humans; Hypertension; Male; Middle Aged; Muscles; Nitroprusside; Oxidative Stress; Reactive Oxygen Species; Sympathetic Nervous System

Cadmium (Cd) is one of the most important environmental pollutants that cause a number of adverse health effects in humans and animals. Recent studies have shown that Cd-induced oxidative damage within the vascular tissues results in vascular dysfunction. The current study was aimed to investigate whether ascorbic acid could protect against Cd-induced vascular dysfunction in mice. Male ICR mice were received CdCl(2) (100 mg/l) via drinking water for 8 weeks alone or received ascorbic acid supplementation at doses of 50 and 100 mg/kg/day for every other day. Results showed that Cd administration increased arterial blood pressure and blunted the vascular responses to vasoactive agents. These alterations were related to increased superoxide production in thoracic aorta, increased urinary nitrate/nitrite, increased plasma protein carbonyl, elevated malondialdehyde (MDA) concentrations in plasma and tissues, decreased blood glutathione (GSH), and increased Cd contents in blood and tissues. Ascorbic acid dose-dependently normalized the blood pressure, improved vascular reactivities to acetylcholine (ACh), phenylephrine (Phe) and sodium nitroprusside (SNP). These improvements were associated with significant suppression of oxidant formation, prevention of GSH depletion, and partial reduction of Cd contents in blood and tissues. The findings in this study provide the first evidence in pharmacological effects of ascorbic acid on alleviation of oxidative damage and improvement of vascular function in a mouse model of Cd-induced hypertension and vascular dysfunction. Moreover, our study suggests that dietary supplementation of ascorbic acid may provide beneficial effects by reversing the oxidative stress and vascular dysfunction in Cd-induced toxicity.

Topics: Animals; Ascorbic Acid; Cadmium; Disease Models, Animal; Hypertension; Male; Mice; Mice, Inbred ICR; Oxidative Stress; Testis; Vascular Diseases

1. Endothelial dysfunction plays a critical role in the development and progression or pathogenesis of hypertension. Amlodipine, a calcium channel blocker, is an effective antihypertensive agent. We investigated the effects of amlodipine on endothelial dysfunction in mesenteric arteries from spontaneously hypertensive rats (SHR). 2. Eight-week-old SHR were treated with amlodipine (10 mg/kg per day) for 8 weeks. Control SHR and Wistar-Kyoto (WKY) rats were treated with saline. Systolic blood pressure (SBP) was measured by the tail-cuff method. Isometric tension changes of isolated mesenteric arterial rings were recorded continuously by a myograph system. Serum contents of malondialdehyde (MDA) and total nitrate/nitrite (NO(x) ) were determined. Vascular superoxide anion production was analysed with dihydroethidium (DHE) fluorescence. 3. The contractile responses to KCl and phenylephrine were greater in untreated SHR than in WKY. Acetylcholine (ACh)-induced relaxation was significantly impaired in untreated SHR. Amlodipine treatment reduced the contractions and improved relaxation to ACh. In WKY, relaxation to ACh was inhibited by N(G) -nitro-l-arginine methyl ester (l-NAME) and not changed by ascorbic acid. In untreated SHR, the response to ACh was unaffected by l-NAME, whereas it was improved by ascorbic acid. Amlodipine restored the inhibitory effect of l-NAME on ACh-induced relaxation, but ascorbic acid no longer exerted its facilitating effect. Amlodipine prevented the rise in SBP and ameliorated abnormalities in serum MDA and NO in untreated SHR. DHE assay showed an increased intravascular superoxide generation in untreated SHR, which was abrogated by amlodipine. 4. Treatment of SHR with amlodipine resulted in amelioration of endothelial dysfunction by anti-oxidant activity and improvement in NO availability.

Topics: Acetylcholine; Amlodipine; Animals; Antihypertensive Agents; Ascorbic Acid; Blood Pressure; Endothelium, Vascular; Hypertension; Male; Malondialdehyde; Mesenteric Arteries; NG-Nitroarginine Methyl Ester; Nitrates; Nitrites; Nitrous Oxide; Phenylephrine; Potassium Chloride; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reactive Oxygen Species; Superoxides

Nitric oxide synthase (NOS) inhibitor asymmetrical dimethylarginine (ADMA) is synthesized by the methylation of arginine as part of the methionine/homocysteine cycle. However, the mechanisms regulating ADMA synthesis in hypertension are unclear.. We investigated the role of ADMA and antioxidants in endothelial dysfunction during methionine-induced homocysteinemia in hypertensives. Thirty-nine hypertensives and forty-nine normotensive controls underwent methionine loading (100 mg methionine/kg BW), after being randomized to receive vitamin C (2 g) and E (800 IU) or placebo. Endothelium-dependent dilation (EDD) was evaluated by plethysmography (baseline and 4-h post-methionine loading (4-h PML)).. Hypertensives had higher homocysteine at baseline (P < 0.001) and 4-h PML (P < 0.05), whereas methionine increased homocysteine in all groups. EDD was decreased in both vitamins and placebo groups in controls (P < 0.01 for both) and vitamins- and placebo-treated hypertensives (P < 0.05 and P < 0.01, respectively). In controls, ADMA was increased in both vitamin- and placebo groups (P < 0.01 for both) at 4-h PML. Hypertensives had higher ADMA at baseline (P < 0.01 vs. normotensive) and remained unchanged at 4-h PML (P = NS in placebo and vitamins treated).. ADMA is elevated in hypertensives but remains unchanged after methionine loading, suggesting that ADMA plays an important role in endothelial dysfunction in hypertensives, but it is not responsible for homocysteine-induced endothelial dysfunction in these patients.

Topics: Adult; Antioxidants; Arginine; Ascorbic Acid; Endothelium, Vascular; Female; Homocysteine; Humans; Hyperhomocysteinemia; Hypertension; Male; Methionine; Middle Aged; Vasodilation; Vitamin E

We compared ascorbic acid (AA) levels in the blood and TPA- and fMLP-stimulated superoxide (O(2)(•-)) production in neutrophils of pre-, early, and late hypertensive stroke-prone spontaneously hypertensive rats (SHRSP) with those of age-matched Wistar Kyoto rats (WKY), or two other normotensive strains of rats. Plasma and lymphocyte AA levels were about two-fold higher in SHRSP as early as 4 weeks old compared to WKY, and also higher than those of Wistar and Sprague-Dawley (SD) rats. Levels of AA were high in the liver and adrenal glands of SHRSP, indicating congenitally high AA levels. The production of O(2)(•-) in neutrophils was about two-fold higher in SHRSP than in WKY even at 4 weeks of age, and increased with age in both strains. Among SHRSP, AA levels in lymphocytes decreased at the late hypertensive stages with a decrease in hepatic l-gulono-γ-lactone oxidase (GLO) activities. These data suggest that bi-phasic AA levels in the blood of SHRSP comprise congenitally high levels and a decrease after persistent hypertension due to enhanced O(2)(•-) production and a decrease in de novo AA synthesis through GLO.

Topics: Adrenal Glands; Aging; Animals; Ascorbic Acid; Disease Models, Animal; Glucose; Hypertension; L-Gulonolactone Oxidase; Liver; Male; Neutrophils; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Rats, Wistar; Risk Factors; Stroke; Superoxides

The effect of fruit and vegetable consumption and blood pressure is unclear. A population-based cross-sectional study was conducted in 20 926 men and women aged 40 to 79 years participating in the European Prospective Investigation Into Cancer-Norfolk who completed a health questionnaire and attended a clinic from 1993 to 1997. The relationship between plasma vitamin C concentrations, as an indicator of fruit and vegetable intake, and systolic BP was examined. The magnitude of their association was assessed using dichotomized values of high (≥140 mm Hg) and low (<140 mm Hg) systolic blood pressure. A total of 20 926 participants (46% men; mean [SD] 58.5 years [9.2 years]) were included after excluding participants with any missing data for variables of interest. People with high vitamin C concentrations had lower clinic blood pressure. The likelihood of having high blood pressure was 22% lower (odds ratio: 0.78 [95% CI: 0.71 to 0.86]) for those who were in the top quartiles of plasma vitamin C levels compared with the bottom quartiles after adjusting for age, sex, body mass index, cholesterol, prevalent medical conditions, smoking, physical activity, alcohol consumption, social class, education, use of vitamin C-containing supplement, and antihypertensive medication. Sex-specific analysis, as well as repeated analysis after exclusion of people who used vitamin C-containing supplements or who were taking antihypertensive medication, did not alter the results. There appears to be a strong association between vitamin C concentrations, an indicator of fruit and vegetable consumption, and a lower level of blood pressure. This may provide further evidence for health benefits of dietary patterns with higher fruit and vegetable consumption.

Topics: Adult; Age Factors; Aged; Ascorbic Acid; Blood Pressure; Cross-Sectional Studies; Europe; Female; Humans; Hypertension; Linear Models; Male; Middle Aged; Multivariate Analysis; Neoplasms; Prospective Studies; Risk Factors; Surveys and Questionnaires; United Kingdom

Some studies have hypothesized the protective role of vitamin C against cardiovascular disorders (CVD) in patients with end-stage renal disease (ESRD). This study was designed to assess plasma vitamin C concentration and its relationship to hemodialysis (HD) patients' morbidity and mortality.. Plasma vitamin C concentrations were assessed in HD patients using spectrophotometry and subjects were prospectively followed for up eighteen months for all-cause mortality. Any association between vitamin C concentration and patients' demographic data, co-morbidities, or the cause of ESRD were investigated using the Chi-square test.. Ninety-one patients with a mean age of 56.7 ± 15.7 years were included in this study. The most frequent cause of ESRD was simultaneous hypertension and diabetes in 30 % of patients, followed by hypertension in 25.6 %, and diabetes in 11.1 %, respectively. About 34 % of patients had CVD as the most prevalent co-morbidity. Forty-nine patients (53.8 %) had low levels of vitamin C concentration. There was a significant relationship between vitamin C insufficiency and presence of any co-morbidity in HD patients (p < 0.05). There was a significant difference in vitamin C concentrations between patients without co-morbidities and those with cardiovascular ones (F[2,88]=3.447, p = 0.036). Twenty-two (24.2 %) patients died over a median duration of 227 days. There was a significant difference in time to death of patients with and without low levels of vitamin C concentration (p = 0.04).. The results showed lower plasma vitamin C levels in HD patients who suffered any co-morbidity and sooner time to death in these patients.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Diseases; Diabetic Nephropathies; Female; Follow-Up Studies; Hospitals, University; Humans; Hypertension; Iran; Kidney Failure, Chronic; Male; Middle Aged; Morbidity; Mortality; Prospective Studies; Renal Dialysis; Survival Analysis; Young Adult

Intermittent hypoxia, a feature of obstructive sleep apnoea, potentiates ventilatory hypoxic responses, alters heart rate variability and produces hypertension, partially owing to an enhanced carotid body responsiveness to hypoxia. Since oxidative stress is a potential mediator of both chemosensory and cardiorespiratory alterations, we hypothesised that an antioxidant treatment may prevent these alterations. Accordingly, we studied the effects of ascorbic acid (1.25 g.L(-1) drinking water) on plasma lipid peroxidation, nitrotyrosine and inducible nitric oxide synthase (iNOS) immunoreactivity in the carotid body, ventilatory and carotid chemosensory responses to acute hypoxia, heart rate variability and arterial blood pressure in male Sprague-Dawley rats exposed to 5% O(2); 12 episodes.h(-1); 8 h.day(-1) or sham condition for 21 days. Intermittent hypoxia increased plasma lipid peroxidation, nitrotyrosine and iNOS expression in the carotid body, enhanced carotid chemosensory and ventilatory hypoxic responses, modified heart rate variability and produced hypertension. Ascorbic acid prevented the increased plasma lipid peroxidation and nitrotyrosine formation within the carotid body, and the enhanced carotid chemosensory and ventilatory responses to hypoxia, as well as heart rate variability alterations and hypertension. The present results support an essential role for oxidative stress in the generation of carotid body chemosensory potentiation and systemic cardiorespiratory alterations induced by intermittent hypoxia.

Topics: Animals; Antioxidants; Ascorbic Acid; Carotid Body; Chemoreceptor Cells; Heart Rate; Hypertension; Hypoxia; Lipid Peroxidation; Lipids; Male; Malondialdehyde; Nitric Oxide Synthase Type II; Nitrosamines; Oxidative Stress; Pulmonary Ventilation; Rats; Sleep Apnea, Obstructive; Tyrosine

In fawn-hooded hypertensive (FHH) rats, a model of hypertension, impaired preglomerular resistance, hyperfiltration, and progressive renal injury, we recently observed that supporting perinatal nitric oxide (NO) availability with the NO donor molsidomine persistently reduced blood pressure (BP) and ameliorated renal injury in male and female offspring. However, beneficial effects of perinatal molsidomine treatment were more pronounced in female than in male FHH rats.. To evaluate whether such protective effects could also be achieved with micronutrients, and whether the gender-dependent differences could be confirmed, we tested perinatal exposure to the micronutrients L-arginine, taurine, vitamin C, and vitamin E (ATCE) in FHH rats. Perinatal micronutrients increased urinary NO metabolite, sodium and potassium excretion only at 4 weeks of age, i.e., at the end of treatment.. From 12 weeks onwards, control males had a significantly higher systolic BP (SBP) than females (P < 0.01); however after perinatal micronutrients, this difference was no longer present, indicating a pronounced antihypertensive effect of perinatal micronutrients in males (interaction P < 0.001). Development of proteinuria was attenuated by perinatal micronutrients in males and females. However, only females showed reduced glomerular filtration rate, filtration fraction, and glomerulosclerosis (GS) after perinatal micronutrients.. In sum, perinatal micronutrients that enhance NO availability ameliorated development of hypertension and proteinuria in FHH rats. Antihypertensive effects were more pronounced in male FHH offspring, whereas renal protective effects were more pronounced in female FHH offspring. Mechanisms underlying gender-specific consequences of perinatal micronutrients require further study.

Topics: Animals; Arginine; Ascorbic Acid; Blood Pressure; Dietary Supplements; Female; Hypertension; Kidney Diseases; Male; Micronutrients; Molsidomine; Nitric Acid; Nitric Oxide Donors; Potassium; Proteinuria; Rats; Rats, Inbred Strains; Sex Factors; Sodium; Taurine; Vitamin E

To ascertain the onset of renal oxidative stress and its interrelation with the increase in blood pressure (BP) and kidney injury in rats subjected to Deoxycorticosterone (DOCA)-salt treatment, BP, renal antioxidants, renal damage indices, and histological changes were studied weekly. In the two other groups, 200 mg/kg/day vitamin E or C were co-administered with DOCA-salt for 4 weeks. Blood Pressure was increased at week one. Urinary N-acetyl-B-diglucosaminidase (NAG) and proteinuria increased and renal catalase decreased at 2nd week. Histological changes and decreased glothatione (GSH) and Ferric reducing antioxidant power (FRAP) were demonstrated at three week. Vitamin therapy increased renal antioxidants and decreased BP, NAG, proteinuria, and histological damage. Thus, elevation in BP precedes the onset of renal oxidative stress in DOCA-salt treated rats. Enhanced renal oxidative stress contributes to kidney damage. In this study, treatment with vitamin C or vitamin E preserved renal antioxidant levels, prevented renal damage, and partially inhibited elevation of BP in the DOCA-salt treatment.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Catalase; Desoxycorticosterone; Glutathione; Hypertension; Kidney; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Sodium Chloride, Dietary; Vitamin E

Underlying cardiovascular disease (CVD) is a risk factor for the exacerbation of air pollution health effects. Pulmonary oxidative stress, inflammation, and altered iron (Fe) homeostasis secondary to CVD may influence mammalian susceptibility to air pollutants. Rodent models of CVD are increasingly used to examine mechanisms of variation in susceptibility. Baseline cardiac and pulmonary disease was characterized in healthy normotensive Wistar Kyoto (WKY) rats, cardiovascular compromised spontaneously hypertensive rats (SHR), and spontaneously hypertensive heart failure (SHHF) rats. Blood pressure, heart rate, and breathing frequencies were measured in rats 11 to 12 wk of age, followed by necropsy at 14 to 15 wk of age. Blood pressure and heart rate were increased in SHR and SHHF relative to WKY rats (SHR > SHHF > WKY). Increased breathing frequency in SHHF and SHR (SHR > SHHF > WKY) resulted in greater minute volume relative to WKY. Bronchoalveolar lavage fluid (BALF) protein and neutrophils were higher in SHHF and SHR relative to WKY (SHHF >> SHR > WKY). Lung ascorbate and glutathione levels were low in SHHF rats. BALF Fe-binding capacity was decreased in SHHF relative to WKY rats and was associated with increased transferrin (Trf) and ferritin. However, lung ferritin was lower and Trf was higher in SHHF relative to WKY or SHR rats. mRNA for markers of inflammation and oxidative stress (macrophage inflammatory protein [MIP]-2, interleukin [IL]-1alpha, and heme oxygenase [HO]-1) were greater in SHHF and SHR relative to WKY rats. Trf mRNA rose in SHR but not SHHF relative to WKY rats, whereas transferrin receptors 1 and 2 mRNA was lower in SHHF rats. Four of 12 WKY rats exhibited cardiac hypertrophy despite normal blood pressure, while demonstrating some of the pulmonary complications noted earlier. This study demonstrates that SHHF rats display greater underlying pulmonary complications such as oxidative stress, inflammation, and impaired Fe homeostasis than WKY or SHR rats, which may play a role in SHHF rats' increased susceptibility to air pollution.

Topics: Animals; Ascorbic Acid; Biomarkers; Bronchoalveolar Lavage Fluid; Cardiovascular Diseases; Disease Models, Animal; Ferritins; Gene Expression; Glutathione; Heart Failure; Hemodynamics; Homeostasis; Hypertension; Inflammation; Iron; Lung; Lung Diseases; Male; Obesity; Oxidative Stress; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Respiratory Function Tests; Stroke; Transferrin

Experimental studies confirmed that reactive oxygen species increase endothelin-1 (ET-1) synthesis, and modulate ET-1 signaling pathway resulting in vasoconstriction and vascular remodeling. The aim of this study was to evaluate the relationship between plasma ET-1 concentration and antioxidant status in patients with essential hypertension and type 2 diabetes mellitus.. 78 hypertensive patients, 53.8% diabetic, mean age 72.1+/-7.07 were examined. The plasma concentration of glucose, creatinine, uric acid, bilirubin, cholesterol, insulin, HbA1c and ET-1 were measured. Antioxidant status was assessed by Ferric Reducing Ability of Plasma (FRAP), vitamin C concentration and erythrocyte superoxide dismutase (SOD) activity.. With diabetes ET-1 concentration was higher (1.35+/-0.51 vs 1.12+/-0.46 pg/mL, p=0.04). The negative correlations between ET-1 concentration and FRAP (r=-0.50, p<0.0001), vitamin C (r=-0.296, p=0.01) and SOD (r=-0.44, p=0.001) were found. Concentration of ET-1 correlated positively with SBP (r=0.33, p=0.005) but not with DBP. The relationship between DBP and ET-1 only in subjects with DBP>110 mm Hg and FRAP<0.40 mmol/L was found. In multiple regression analysis plasma ET-1 levels were associated independently with FRAP (beta=-0.583, p=0.003) and plasma vitamin C (beta=-0.407, p=0.04).. In hypertensive and diabetic patients higher plasma endothelin-1 level was independently associated with lower plasma antioxidant status measured by FRAP and decreased vitamin C concentration, which may be a result of increased oxidative stress in these diseases.

Topics: Aged; Antihypertensive Agents; Antioxidants; Ascorbic Acid; Blood Pressure; Diabetes Mellitus, Type 2; Endothelin-1; Erythrocytes; Female; Humans; Hypertension; Male; Protein Kinases; Regression Analysis; Superoxide Dismutase; TOR Serine-Threonine Kinases

Higher uric acid levels are associated with an increased risk for developing hypertension. Higher intake of fructose increases plasma uric acid levels and higher intake of vitamin C reduces uric acid levels, but whether these nutrients are independently associated with the risk for developing hypertension is unknown. We studied this question by analyzing data from participants of three large and independent prospective cohorts: Nurses' Health Study 1 (n = 88,540), Nurses' Health Study 2 (n = 97,315), and the Health Professionals Follow-up Study (n = 37,375). Relative risks and 95% confidence intervals for incident hypertension were computed according to quintiles of fructose intake and categories of vitamin C intake using multivariable Cox proportional hazards regression. Fructose intake was not associated with the risk for developing hypertension; the multivariable relative risks (95% confidence intervals) for the highest compared with the lowest quintile of fructose intake were 1.02 (0.99 to 1.06) in Nurses' Health Study 1, 1.03 (0.98 to 1.08) in Nurses' Health Study 2, and 0.99 (0.93 to 1.05) in Heath Professionals Follow-up Study. Regarding vitamin C, the relative risks for individuals who consumed > or =1500 mg/d compared with those who consumed <250 mg/d were 0.89 (0.83 to 0.96) in Nurses' Health Study 1, 1.02 (0.91 to 1.14) in Nurses' Health Study 2, and 1.06 (0.97 to 1.15) in Health Professionals Follow-up Study. In conclusion, fructose and vitamin C intake do not substantially influence the risk for developing hypertension.

Topics: Adult; Alcohol Drinking; Ascorbic Acid; Beverages; Body Mass Index; Coffee; Cohort Studies; Energy Intake; Fructose; Humans; Hypertension; Middle Aged; Proportional Hazards Models; Risk; Risk Factors; Uric Acid

We assessed whether co-supplementation of vitamins C and E has additive beneficial effects on reducing the kidney damage and attenuation of the arterial pressure elevation compared to administration of either vitamin C or vitamin E alone in deoxycorticosterone acetate-salt-induced hypertension.. Forty rats were divided into 4 study groups and 1 sham-operated group. Unilateral nephrectomy was carried out in the study groups and hypertension was induced by deoxycorticosterone injection and 1% sodium chloride and 0.2% potassium chloride added to the drinking water. Vitamins C and E (200 mg/kg/day) or combination of them were administered with DOCA-salt for 4 weeks in 3 study groups. The effects of DOCA and salt and treatment with vitamins were compared in terms of blood pressure, urinary protein excretion, antioxidant activity of the kidneys, and renal histological changes.. Four weeks of supplementations of vitamins C, vitamin E, and both in the DOCA-salt-treated rats had comparable significant effects in decreasing systolic blood pressure. Urinary protein excretion and histological damage did not significantly change with the combination therapy of vitamins C and E compared to the vitamin C or E alone. The renal levels of glutathione and ferric reducing/antioxidant power in combination therapy group were similar to the two other treatment groups and were significantly higher than non-treated group.. Co-administration of vitamin C and E does not have an additive beneficial effect on reducing the kidney damage and hypertension compared to either vitamin C or E alone in DOCA-salt-induced hypertension.

Topics: Animals; Antioxidants; Ascorbic Acid; Calcium Chloride; Desoxycorticosterone; Dietary Supplements; Disease Models, Animal; Drug Therapy, Combination; Hypertension; Kidney Diseases; Male; Potassium Chloride; Rats; Rats, Sprague-Dawley; Vitamin E

Postischemic acute renal failure is worsened when occurs in a various conditions with impaired nitric oxide (NO) synthesis, such as arterial hypertension. Reoxygenation itself increases ischemic injury through the massive production of oxygen-free radicals. Therefore, we have directed our investigations to effects of both NO donor and antioxidant treatment on course of acute renal failure in experimental hypertension. Experiments were performed in anesthetized, adult male spontaneously hypertensive rats. In ARF groups the right kidney was removed, and rats were subjected to renal ischemia by clamping the left renal artery for 40 min. Experimental group received NO donor L-arginine (2 g/kg b.m.) (LArg group), or oxidant scavenger vitamin C (100 mg/kg b.m.) (Vit C group) during 3 days before the period of ischaemia. All parameters were measured 24 h after reperfusion. The mean arterial pressure was markedly reduced and renal vascular resistance significantly dropped in the ARF+L-Arg group vs. ARF group. Tubular injuries were similar between the ARF+L-Arg and ARF groups. Intensity of tubular necrosis and dilatation was markedly reduced in ARF+Vit C group in comparison to ARF. L-arginine failed to reduce tubular injury, despite its evident improvement of systemic and renal haemodynamic, thus NO seems to act as a double-egged sword, but reduction of tubular injury promotes vitamin C as an effective chemoprotectant against ishemia-reperfusion tubular injury in hypertension.

Topics: Animals; Antioxidants; Arginine; Ascorbic Acid; Hemodynamics; Hypertension; Kidney; Male; Nitric Oxide; Rats; Rats, Inbred SHR; Renal Insufficiency; Reperfusion Injury

The prevalence of hypertension and its contribution to cardiovascular disease risk makes it imperative to identify factors that may help prevent this disorder. Extensive biological and biochemical data suggest that plasma ascorbic acid may be such a factor. In this study we examined the association between plasma ascorbic acid concentration and blood pressure (BP) in young-adult women.. Participants were 242 Black and White women aged 18-21 yr from the Richmond, CA, cohort of the National Heart, Lung and Blood Institute Growth and Health Study. We examined the associations of plasma ascorbic acid with BP at follow-up year 10, and with change in BP during the previous year.. In cross-sectional analysis, plasma ascorbic acid at year 10 was inversely associated with systolic BP and diastolic BP after adjusting for race, body mass index, education, and dietary intake of fat and sodium. Persons in the highest one-fourth of the plasma ascorbic acid distribution had 4.66 mmHg lower systolic BP (95% CI 1.10 to 8.22 mmHg, p = 0.005) and 6.04 mmHg lower diastolic BP (95% CI 2.70 to 9.38 mmHg, p = 0.0002) than those in the lowest one-fourth of the distribution. In analysis of the change in BP, plasma ascorbic acid was also inversely associated with change in systolic BP and diastolic BP during the previous year. While diastolic blood pressure among persons in the lowest quartile of plasma ascorbic acid increased by 5.97 mmHg (95% CI 3.82 to 8.13 mmHg) from year 9 to year 10, those in the highest quartile of plasma vitamin C increased by only 0.23 mmHg (95% CI -1.90 to +2.36 mmHg) (test for linear trend: p < 0.0001). A similar effect was seen for change in systolic BP, p = 0.005.. Plasma ascorbic acid was found to be inversely associated with BP and change in BP during the prior year. The findings suggest the possibility that vitamin C may influence BP in healthy young adults. Since lower BP in young adulthood may lead to lower BP and decreased incidence of age-associated vascular events in older adults, further investigation of treatment effects of vitamin C on BP regulation in young adults is warranted.

Topics: Adolescent; Ascorbic Acid; Blood Pressure; Cohort Studies; Cross-Sectional Studies; Female; Humans; Hypertension; Risk Factors; Young Adult

Inappropriate response of the carotid body region to encroachment of its perfusion results in essential hypertension (EH) and/or non-insulin dependent diabetes mellitus (NIDDM). This encroachment is caused by atherosclerosis. The carotid body perceives the encroachment on the lumen as a reduction in the availability of oxygen and glucose for the brain. Raising the perfusion pressure (thus, resulting in EH) and/ or inducing insulin resistance (causing NIDDM) are seen as compensatory mechanisms in response to the primary pathology, ie the encroachment of the lumen by atherosclerosis. Therefore, the reduction or reversal of the atherosclerosis process will help improve perfusion to the carotid bodies, which will in turn reduce or reverse the pathophysiological compensatory adjustments described above. A supplemental therapy, in addition to the standard treatment, with vitamin C is suggested here. The argument in favour of this suggestion is the basis of this paper. Vitamin C is a very important antioxidant. It is suggested to be used without any interference with the usual therapy prescribed for these two chronic diseases. It is recommended to be administered in small, frequent doses of 100mg every 2h, except during sleep. There is no need for compensation for the occasional missed dose. The safety of larger doses of vitamin C than the current recommendations, represents the beauty and is reassuring in recommending this approach.

Topics: Antioxidants; Ascorbic Acid; Diabetes Mellitus, Type 2; Humans; Hypertension; Models, Cardiovascular

Cardiovascular risk is increased among HIV-infected patients receiving antiretroviral therapy due to the development of hypertension and metabolic abnormalities. In this study, we investigated the effects of long-term treatment with zidovudine (AZT) and vitamin C, alone and in combination, on blood pressure and on the chain of events linking oxidative stress to cardiac damage in the rat.. Six adult Wistar Kyoto rats received AZT (1 mg/ml) in the drinking water for 8 months, six vitamin C (10 g/kg of food) and AZT, six vitamin C alone, and six served as controls.. AZT increased systolic blood pressure, expression of gp91(phox) and p47(phox) subunits of NAD(P)H oxidase, and protein kinase C (PKC) delta activation and reduced antioxidant power of plasma and cardiac homogenates. AZT also caused morphological alterations in cardiac myocyte mitochondria, indicative of functional damage. All of these effects were prevented by vitamin C.. Chronic AZT administration increases blood pressure and promotes cardiovascular damage through a NAD(P)H oxidase-dependent mechanism that involves PKC delta. Vitamin C antagonizes these adverse effects of AZT in the cardiovascular system.

Topics: Animals; Antimetabolites; Antioxidants; Ascorbic Acid; Blotting, Western; Enzyme Activation; Hypertension; Male; Membrane Glycoproteins; Microscopy, Electron; Myocytes, Cardiac; NADPH Oxidase 2; NADPH Oxidases; Nuclear Proteins; Protein Kinase C; Rats; Rats, Inbred WKY; Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; Vitamins; Zidovudine

Full expression of reflex cutaneous vasodilation (VD) is dependent on nitric oxide (NO) and is attenuated with essential hypertension. Decreased NO-dependent VD may be due to 1) increased oxidant stress and/or 2) decreased L-arginine availability through upregulated arginase activity, potentially leading to increased superoxide production through uncoupled NO synthase (NOS). The purpose of this study was to determine the effect of antioxidant supplementation (alone and combined with arginase inhibition) on attenuated NO-dependent reflex cutaneous VD in hypertensive subjects. Nine unmedicated hypertensive [HT; mean arterial pressure (MAP) = 112 +/- 1 mmHg] and nine age-matched normotensive (NT; MAP = 81 +/- 10 mmHg) men and women were instrumented with four intradermal microdialysis (MD) fibers: control (Ringer), NOS inhibited (NOS-I; 10 mM N(G)-nitro-L-arginine), L-ascorbate supplemented (Asc; 10 mM L-ascorbate), and Asc + arginase inhibited [Asc+A-I; 10 mM L-ascorbate + 5 mM (S)-(2-boronoethyl)-L-cysteine-HCl + 5 mM N(omega)-hydroxy-nor-L-arginine]. Oral temperature was increased by 0.8 degrees C via a water-perfused suit. N(G)-nitro-L-arginine was then ultimately perfused through all MD sites to quantify the change in VD due to NO. Red blood cell flux was measured by laser-Doppler flowmetry over each skin MD site, and cutaneous vascular conductance (CVC) was calculated (CVC = flux/MAP) and normalized to maximal CVC (%CVC(max); 28 mM sodium nitroprusside + local heating to 43 degrees C). During the plateau in skin blood flow (Delta T(or) = 0.8 degrees C), cutaneous VD was attenuated in HT skin (NT: 42 +/- 4, HT: 35 +/- 3 %CVC(max); P < 0.05). Asc and Asc+A-I augmented cutaneous VD in HT (Asc: 57 +/- 5, Asc+A-I: 53 +/- 6 %CVC(max); P < 0.05 vs. control) but not in NT. %CVC(max) after NOS-I in the Asc- and Asc+A-I-treated sites was increased in HT (Asc: 41 +/- 4, Asc+A-I: 40 +/- 4, control: 29 +/- 4; P < 0.05). Compared with the control site, the change in %CVC(max) within each site after NOS-I was greater in HT (Asc: -19 +/- 4, Asc+A-I: -17 +/- 4, control: -9 +/- 2; P < 0.05) than in NT. Antioxidant supplementation alone or combined with arginase inhibition augments attenuated reflex cutaneous VD in hypertensive skin through NO- and non-NO-dependent mechanisms.

Topics: Administration, Cutaneous; Antioxidants; Arginase; Ascorbic Acid; Blood Flow Velocity; Blood Vessels; Boronic Acids; Case-Control Studies; Enzyme Inhibitors; Female; Fever; Humans; Hypertension; Laser-Doppler Flowmetry; Male; Microdialysis; Middle Aged; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Reflex; Skin; Time Factors; Vasodilation

The goal of this study was to test the hypothesis that increases in oxidative stress in Dahl S rats on a high-salt diet help to stimulate renal nuclear factor-kappaB (NF-kappaB), renal proinflammatory cytokines, and chemokines, thus contributing to hypertension, renal damage, and dysfunction. We specifically studied whether antioxidant treatment of Dahl S rats on high Na intake would decrease renal inflammation and thus attenuate the hypertensive and adverse renal responses. Sixty-four 7- to 8-wk-old Dahl S or R/Rapp strain rats were maintained for 5 wk on high Na (8%) or high Na + vitamins C (1 g/l in drinking water) and E (5,000 IU/kg in food). Arterial and venous catheters were implanted at day 21. By day 35 in the high-Na S rats, antioxidant treatment significantly increased the renal reduced-to-oxidized glutathione ratio and decreased renal cortical H(2)O(2) and O(2)(*-) release and renal NF-kappaB. Antioxidant treatment with vitamins C and E in high-Na S rats also decreased renal monocytes/macrophages in the glomeruli, cortex, and medulla, decreased tumor necrosis factor-alpha by 39%, and decreased monocyte chemoattractant protein-1 by 38%. Vitamin-treated, high-Na S rats also experienced decreases in arterial pressure, urinary protein excretion, renal tubulointerstitial damage, and glomerular necrosis and increases in glomerular filtration rate and renal plasma flow. In conclusion, antioxidant treatment of high-Na Dahl S rats decreased renal inflammatory cytokines and chemokines, renal immune cells, NF-kappaB, and arterial pressure and improved renal function and damage.

Topics: Animals; Anti-Inflammatory Agents; Antihypertensive Agents; Antioxidants; Ascorbic Acid; Blood Pressure; Chemokine CCL2; Disease Models, Animal; Glomerular Filtration Rate; Glutathione; Heart Rate; Hydrogen Peroxide; Hypertension; Inflammation; Interleukin-6; Kidney; Macrophages; Monocytes; NF-kappa B; Oxidative Stress; Proteinuria; Rats; Rats, Inbred Dahl; Renal Circulation; Sodium Chloride, Dietary; Superoxides; Time Factors; Tumor Necrosis Factor-alpha; Vitamin E

This study examined whether the anti-oxidants ascorbic acid, alpha- or gamma-tocopherol, could modify adrenocorticotrophic hormone (ACTH)-hypertension in Sprague-Dawley rats, a model associated with increased oxidative stress. Systolic blood pressure (SBP) was measured by the tail-cuff method. After four days of ascorbic acid (AA) (200 mg/kg/day drinking) or alpha-tocopherol (500 mg/kg/d i.p. or feed), rats were co-administered ACTH (0.2 mg/kg/day s.c.) or saline for 11 days (prevention studies). In reversal studies, ACTH/saline was administered for 15 days, and from day 9, alpha- or gamma-tocopherol (20 mg/kg/day) was added. ACTH increased SBP compared to saline (p < 0.05). AA or alpha-tocopherol failed to prevent and alpha- or gamma-tocopherol failed to reverse ACTH-induced hypertension. Thus, neither vitamin C (water soluble) nor E (lipid soluble) modified ACTH-induced hypertension in the rat.

Topics: Adrenocorticotropic Hormone; Animals; Antioxidants; Ascorbic Acid; Disease Models, Animal; Hypertension; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Systole; Tocopherols; Vitamins

We studied the effects of antioxidants resveratrol and pQ510 on physiological parameters and the state of endothelial NO-synthase as a marker of the regulatory function of the endothelium in the aorta of rats with modeled arterial hypertension. The antioxidants promoted recovery of stable NO metabolites in rat serum and maintained expression of endothelial NO-synthase at a normal level. These effects were confirmed by correction of blood pressure and endothelium-dependent vascular dilation assessed by endothelial dysfunction coefficient.

Topics: Animals; Antioxidants; Ascorbic Acid; Endothelium, Vascular; Hypertension; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Organometallic Compounds; Rats; Rats, Wistar; Resveratrol; Stilbenes

This study investigated the association of blood pressure with blood oxidative stress-related parameters in normotensive and hypertensive subjects. A cross-sectional design was applied to 31 hypertensive patients and 35 healthy normotensive subjects. All subjects were men between the ages of 35 and 60 years. Exclusion criteria were obesity, dyslipidemia, diabetes mellitus, smoking and current use of any medication. All patients underwent 24-h ambulatory blood pressure monitoring and sampling of blood and urine. Antioxidant enzymes activity, reduced/oxidized glutathione ratio (GSH/GSSG), and lipid peroxidation (malondialdehyde) were determined in erythrocytes. Parameters measured in the plasma of test subjects were plasma antioxidant status, lipid peroxidation (8-isoprostane), plasma vitamin C and E, and the blood pressure modulators renin, aldosterone, endothelin-1 and homocysteine. Daytime systolic and diastolic blood pressures of hypertensives were negatively correlated with plasma antioxidant capacity (r=-0.46, p<0.009 and r=-0.48, p<0.007), plasma vitamin C levels (r=-0.53, p<0.003 and r=-0.44, p<0.02), erythrocyte activity of antioxidant enzymes, and erythrocyte GSH/GSSG ratio, with hypertensives showing higher levels of oxidative stress. Blood pressures showed a positive correlation with both plasma and urine 8-isoprostane. Neither plasma vitamin E nor the assessed blood pressure modulator levels showed significant differences between the groups or correlation with blood pressures. These findings demonstrate a strong association between blood pressure and some oxidative stress-related parameters and suggest a possible role of oxidative stress in the pathophysiology of essential hypertension.

Topics: Adult; Aldosterone; Ascorbic Acid; Blood Pressure; Cross-Sectional Studies; Dinoprost; Endothelin-1; Glutathione; Homocysteine; Humans; Hypertension; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Renin; Vitamin E

Endothelial dysfunction and underperfusion of exercising muscle contribute to exercise intolerance, hyperventilation, and breathlessness in atrial fibrillation (AF). Cardioversion (CV) improves endothelial function and exercise performance. We examined whether CV is equally beneficial in diabetes and hypertension, diseases that cause endothelial dysfunction and are often associated with AF. Cardiopulmonary exercise and pulmonary and endothelial (brachial artery flow-mediated dilation) function were tested before and after CV in patients with AF alone (n = 18, group 1) or AF with hypertension (n = 19, group 2) or diabetes (n = 19, group 3). Compared with group 1, peak exercise workload, O2 consumption (Vo2), O2 pulse, aerobic efficiency (Delta Vo2/Delta WR), and ratio of brachial diameter changes to flow changes (Delta D/Delta F) were reduced in group 2 and, to a greater extent, in group 3; exercise ventilation efficiency (Ve/Vco2 slope) and dead space-to-tidal volume ratio (Vd/Vt) were similar among groups. CV had less effect on peak workload (+7% vs. +18%), peak Vo2 (+12% vs. +17%), O2 pulse (+33% vs. +50%), Delta Vo2/Delta WR (+7% vs. +12%), Ve/Vco2 slope (-6% vs. -12%), Delta D/Delta F (+7% vs. +10%), and breathlessness (Borg scale) in group 2 than in group 1 and was ineffective in group 3. The antioxidant vitamin C, tested in eight additional patients in each cohort, improved flow-mediated dilation in groups 1 and 2 before, but not after, CV and was ineffective in group 3, suggesting that the oxidative injury is least in lone AF, greater in hypertension with AF, and greater still in diabetes with AF. Comorbidities that impair endothelial activity worsen endothelial dysfunction and exercise intolerance in AF. The advantages of CV appear to be inversely related to the extent of the underlying oxidative injury.

Topics: Aged; Antioxidants; Ascorbic Acid; Atrial Fibrillation; Brachial Artery; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 2; Echocardiography; Electric Countershock; Endothelium, Vascular; Exercise Test; Female; Humans; Hypertension; Male; Middle Aged; Myocytes, Cardiac; Reactive Oxygen Species; Regional Blood Flow

To study the possible involvement of an (im)balance between oxidants and antioxidants in pre-eclampsia concentrations of intra- and extracellular blood antioxidants in women with uncomplicated and hypertensive pregnancies, they were studied preconceptionally and throughout pregnancy.. In uncomplicated pregnancies (n = 19) and hypertensive pregnancies (n = 6) concentrations of whole blood and plasma thiols, plasma vitamins/E and C, hemoglobin, and hematocrit were assessed at preconception, 6, 10, 20, and 37 weeks of gestational age, as well as six weeks postpartum. A repeated mixed model was used for statistical analysis.. Vitamin C and most whole blood and plasma thiol concentrations decreased during pregnancy, while vitamin E, whole blood oxidized cysteinyl-glycine and the ratio of free to oxidized homocysteine revealed a linear increase during pregnancy. Postpartum plasma cysteine and vitamin C levels and the ratio of free to oxidized levels of cysteine, cysteinyl-glycine, and glutathione were significantly (p <0.05) lower as compared to preconceptional levels, whereas whole blood oxidized cysteine, cysteinyl-glycine and glutathione levels, and whole blood and plasma homocysteine levels were significantly (p <0.05) higher six weeks after delivery. Plasma cysteine and homocysteine, and whole blood oxidized cysteine and homocysteine levels were significantly (p <0.05) higher at 37 weeks of gestational age in the hypertensive group compared to those in the uncomplicated group. There were no other differences between the hypertensive and uncomplicated groups.. In normal pregnancy there seems a balance between antioxidant and oxidant concentrations despite modest oxidative stress. In mildly hypertensive pregnancies a marginal imbalance may occur.

Topics: Adult; Antioxidants; Ascorbic Acid; Female; Hematocrit; Hemoglobins; Humans; Hypertension; Longitudinal Studies; Pregnancy; Pregnancy Complications, Cardiovascular; Statistics, Nonparametric; Sulfhydryl Compounds; Vitamin E

Accumulation of advanced glycation end-products (AGEs) has been implicated in the pathogenesis of chronic transplant dysfunction and cardiovascular disease in renal transplant recipients. We aimed to investigate which factors are associated with tissue AGE accumulation in renal transplant recipients.. The AGE accumulation was assessed using a validated skin-autofluorescence reader (AFR) in 285 consecutive renal transplant recipients (57% male, aged 50+/-12 years) visiting the outpatient clinic at a median (interquartile range) time of 73 (32-143) months after transplantation. Furthermore, various transplant- and recipient-related factors of interest were collected.. Average skin-autofluorescence of lower arm and leg was 2.7+/-0.8 a.u. Skin-autofluorescence was positively determined by recipient age, systolic blood pressure, smoking, high-sensitivity C-reactive protein, duration of pre-transplant dialysis, and negatively by plasma vitamin C levels, creatinine clearance at baseline, and change in creatinine clearance since one year after transplantation in linear multivariate regression analysis. Together, these factors explained 41% of the variance of skin-autofluorescence.. Skin-autofluorescence was associated with several risk factors for cardiovascular disease and chronic renal transplant dysfunction. These results are in line with the hypothesis that AGEs play a role in the pathogenesis of these conditions in renal transplant recipients. Prospective studies are required to investigate whether the AFR can be used as a simple, non-invasive tool to identify and monitor patients at risk for chronic renal transplant dysfunction and cardiovascular disease.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Ascorbic Acid; C-Reactive Protein; Cardiovascular Diseases; Comorbidity; Creatinine; Delayed Graft Function; Diabetes Complications; Female; Fluorometry; Forearm; Glycated Hemoglobin; Glycation End Products, Advanced; Histocompatibility; Humans; Hypercholesterolemia; Hypertension; Immunosuppressive Agents; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Leg; Linear Models; Male; Middle Aged; Obesity; Risk Factors; Skin; Smoking; Vitamin E

It has not been completely demonstrated if hypertension may, in part, develop as a result of increased oxidative stress (OS), inflammation and little is known about the short-term effects of antioxidant therapy. This study was designed to appreciate the effect of 7 days vitamin C-enriched diet (5 g/kg/day) on hemodynamic function and vascular OS in normotensive Wistar Kyoto rats and hypertensive rats (SHR). Aorta NAD(P)H oxidase activity was determinate and free radicals evaluated by electron spin resonance with a spin probe CP-H. Matrix metalloproteinase-1 (MMP-1) and monocyte chemoattractant protein-1 (MCP-1) expression were measured. The treatment with vitamin C did not change arterial pressure in SHR but prevented the increase in OS levels in SHR aortas. MMP-1 and MCP-1 expressions were more intense in the media of SHR aortas than in those of WKY rats but these expressions were not modified by vitamin C-pretreatment. Vitamin C-pretreatment was not able to protect heart against in vitro ischemia-reperfusion dysfunctions. These data may suggest that treatment with high doses of vitamin C in SHR can limit over-production of reactive oxygen species; however this effect was not accompanied with changes in arterial pressure and protection against I-R dysfunctions. Dissociation between vascular oxidative stress and cardiovascular function may be evoked.

Topics: Animals; Antioxidants; Aorta; Ascorbic Acid; Blood Pressure; Chemokine CCL2; Heart; Hypertension; Male; Matrix Metalloproteinase 1; NADPH Oxidases; Organ Culture Techniques; Oxidative Stress; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reperfusion Injury; Time Factors

Impaired vascular reactivity is a hallmark of several cardiovascular diseases that include hypertension and diabetes. This study compared the changes in vascular reactivity in age-matched experimental hypertension and diabetes, and, subsequently, tested whether these changes could be affected directly by ascorbic acid (10 microM). Endothelium-derived nitric oxide (NO) modulation of ascorbic acid effects was also investigated. All the experiments were performed in the presence of a cyclooxygenase inhibitor, indomethacin (10 microM). Results showed that the endothelium-dependent and -independent relaxations induced by acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were blunted to a similar extent in isolated aortic rings from age-matched spontaneously hypertensive (SHR) (R(max): ACh = 72.83+/-1.86%, SNP = 96.6+/-1.90%) and diabetic (Rmax: ACh = 64.09+/-5.14%, SNP = 95.84+/-1.41%) rats compared with aortic rings of normal rats (Rmax: ACh = 89%, SNP = 104.0+/-1.0%). The alpha1-receptor-mediated contractions induced by phenylephrine (PE) were augmented in diabetic (Cmax = 148.8+/-9.0%) rat aortic rings compared to both normal (Cmax = 127+/-6.9%) and SHR (Cmax = 118+/-4.5%) aortic rings. Ascorbic acid pretreatment was without any significant effects on the vascular responses to ACh, SNP and PE in aortic rings from normal rats. Ascorbic acid significantly improved ACh-induced relaxations in SHR (Rmax = 89.09+/-2.82%) aortic rings to a level similar to that observed in normal aortic rings, but this enhancement in ACh-induced relaxations was only partial in diabetic aortic rings. Ascorbic acid lacked any effects on SNP-induced relaxations in both SHR and diabetic aortic rings. Ascorbic acid markedly attenuated contractions induced by PE in aortic rings from both SHR (Cmax = 92.9+/-6.68%) and diabetic (Cmax = 116.9+/-9.4%) rats. Additionally, following inhibition of nitric oxide synthesis with l-NAME, ascorbic acid attenuated PE-induced contractions in all aortic ring types studied. These results suggest that (1) vascular hyper-responsiveness to alpha(1)-receptor agonists in diabetic arteries is independent of endothelial nitric oxide dysfunction; (2) ascorbic acid directly modulates contractile responses of hypertensive and diabetic rat aortas, likely through mechanisms in part independent of preservation of endothelium-derived nitric oxide.

Topics: Acetylcholine; Age Factors; Animals; Aorta, Thoracic; Ascorbic Acid; Diabetes Mellitus, Experimental; Epinephrine; Hypertension; Male; Nitroprusside; Rats; Rats, Inbred WKY; Vasoconstriction

Exercising muscle hypoperfusion stimulates afferents (metaboreceptors) involved in the regulation of ventilation. Atrial fibrillation (AF), particularly when combined with diseases causing endothelial (ED) impairment, such as hypertension (HP) and diabetes mellitus (DM), depresses the ED activity and enhances exercise hyperventilation. The relationship between these two functions and the underlying mechanisms have not been explored previously. In lone AF or AF associated with HP or DM (12 subjects in each cohort), we investigated the brachial artery flow-mediated dilatation (ED function) and ventilation during the recovery phase of handgrip (metaboreflex) exercise for subjects receiving placebo or oral vitamin C (double-blind crossover), both before and after cardioversion (CV) to sinus rhythm. Baseline ED impairment was increasingly more severe and the ergoreflex activity more pronounced in AF + HP and AF + DM compared with lone AF. Vitamin C and CV significantly improved both flow-mediated dilatation and metaboreflex activity in lone AF and AF + HP, and vitamin C did not produce any additive effect when administered after CV. In AF + DM, neither vitamin C nor CV was effective. This study provides the following information: AF generates oxidative injury, which is less when the arrhythmia is lone AF and greater when the arrhythmia is associated with HP. In DM, the oxidative injury generated by AF is refractory to a rather weak antioxidant, like vitamin C, or the baseline damage is such as to prevent any additive influence of AF. In AF, a cause-effect link exists between ED dysfunction and metaboreflex activity. Ventilatory advantages of CV seem to be inversely related with the extension of the underlying ED oxidative impairment.

Topics: Aged; Antioxidants; Ascorbic Acid; Atrial Fibrillation; Brachial Artery; Diabetes Complications; Diabetes Mellitus, Type 2; Double-Blind Method; Echocardiography; Electric Countershock; Endothelium, Vascular; Exercise; Female; Humans; Hypertension; Male; Middle Aged; Reflex; Regional Blood Flow

We assessed the role of cytochrome P450 2C9 (CYP 2C9)-derived endothelium-derived hyperpolarizing factor (EDHF) in the forearm microcirculation of essential hypertensive patients (EH) by utilizing sulfaphenazole (SUL), a selective CYP 2C9 inhibitor.. In EH patients, EDHF acts as a compensatory pathway when nitric oxide (NO) availability is reduced. Cytochrome P450 2C9 is a possible source of EDHF.. In 36 healthy subjects (normotensive [NT]) and 32 hypertensive patients (HT), we studied forearm blood flow (strain-gauge plethysmography) changes induced by intraarterial acetylcholine (ACH) and bradykinin (BDK), repeated during N(G)-monomethyl-L-arginine (L-NMMA) (100 mug/100 ml/min) or SUL (0.03 mg/100 ml/min). In HT, the effect of SUL on ACH and BDK was repeated during vitamin C (8 mg/100 ml/min). Sodium nitroprusside (SNP) was utilized as control.. In NT, vasodilation to ACH and BDK was blunted by L-NMMA and not changed by SUL. In contrast, in HT responses to ACH and BDK, reduced compared with NT, were resistant to L-NMMA. In these patients, SUL blunted vasodilation to ACH and to a greater extent the response to BDK. When retested with vitamin C, SUL was no longer effective on both endothelial agonists. In 2 final groups of normotensive control subjects, vasodilation to ACH or BDK residual to cyclooxygenase and L-NMMA blockade was further inhibited by simultaneous SUL infusion. Response to SNP, similar between NT and HT, was unaffected by SUL.. Cytochrome P450 epoxygenase-derived EDHF acts as a partial compensatory mechanism to sustain endothelium-dependent vasodilation in HT, particularly the BDK-mediated response, when NO activity is impaired because of oxidative stress.

Topics: Acetylcholine; Adult; Aryl Hydrocarbon Hydroxylases; Ascorbic Acid; Biological Factors; Bradykinin; Case-Control Studies; Cytochrome P-450 CYP2C9; Drug Combinations; Drug Synergism; Endothelium, Vascular; Enzyme Inhibitors; Female; Forearm; Humans; Hypertension; Male; Microcirculation; Middle Aged; Nitroprusside; omega-N-Methylarginine; Regional Blood Flow; Sulfaphenazole; Vasodilation; Vasodilator Agents

The goal of this study was to test the hypothesis that oxidative stress in Dahl salt-sensitive (SS) rats on a high-sodium intake contributes to the progression of renal damage, the decreases in renal hemodynamics, and the development of hypertension. We specifically studied whether antioxidant therapy, using vitamins C and E, could help prevent renal damage and glomerular filtration rate (GFR) and renal plasma flow reductions and attenuate the increases in arterial pressure. Thirty-three 7- to 8-week old Dahl SS/Rapp strain rats were placed on either a high-sodium (8%) or a low-sodium (0.3%) diet with or without vitamin E (111 IU/d) in the food and 98 mg/d vitamin C in the drinking water for 5 weeks. Rats were equipped with indwelling arterial and venous catheters at day 21. By day 35 in the rats with high-sodium diet, vitamin C and E treatment significantly decreased renal cortical and medullary O2*- release, mean arterial pressure, urinary protein excretion, glomerular necrosis, and renal tubulointerstitial damage. At this time, GFR significantly decreased in the high-sodium diet group (1.6+/-0.2 mL/min) when compared with either the high-sodium plus vitamins C and E (2.9+/-0.2 mL/min) or the low-sodium diet group (2.9+/-0.3 mL/min). In SS rats on high-sodium diet, renal plasma flow decreased 40%, and this reduced flow was restored by vitamin treatment. In Dahl salt-sensitive hypertension, increased oxidative stress plays an important role in the renal damage, decreases in renal hemodynamics, and increases in arterial pressure that occur. Antioxidant treatment with vitamins C and E improves renal dysfunction, lessens renal injury, and decreases arterial pressure in Dahl salt-sensitive hypertension.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Heart Rate; Hemodynamics; Hypertension; Kidney; Kidney Cortex; Kidney Diseases; Kidney Medulla; Male; Proteinuria; Rats; Rats, Inbred Dahl; Renal Circulation; Sodium Chloride; Superoxides; Vitamin E

Traditional risk factors do not appear to explain fully the variation in the incidence of the cardiovascular diseases (CVD). Epidemiological studies have not been entirely consistent with regard to the relationship between antioxidant vitamin intake and CVD and there appears to be little data on this relationship in non-Caucasian populations. This study aimed to investigate the dietary intake of vitamin A, C, and vitamin E, and carotenoids, serum concentrations of vitamin E and A and indices of lipid peroxidation were measured in male Saudi patients with established CVD and age-matched controls. We assessed the dietary intakes of vitamins A, C, and E and carotenoids, by a food frequency questionnaire. Serum vitamins A and E concentrations were measured by HPLC, in 130 Saudi male subjects with established CVD, and 130 age-matched controls. We also determined serum lipid profiles (total cholesterol, triglycerides, HDL-C, LDL-C), lipoprotein (a), oxidized LDL, and serum lipid peroxide concentrations. Diabetes mellitus (P<0.0001), a positive smoking habit (P<0.0001) and hypertension (P<0.05) were more prevalent among CVD patients. Levels of dietary vitamin E and A were also significantly higher among cases. In conditional logistic regression analysis, the most significant characteristics differentiating CVD patients from controls were diabetes mellitus (Odds ratio 2.49, CI 1.42-4.37, P<0.001), total fat intake (Odds ratio 1.02, CI 1.01-1.03, P<0.01), serum vitamin A (Odds ratio 0.72, CI 0.53-0.99, P<0.05), and the vitamin A/total fat intake ratio (Odds ratio 1.04, CI 1.01-1.06, P<0.01). In a Saudi population, smoking habit and hypertension were significantly more common among patients with CVD. Multivariate analysis showed that dietary total fat and vitamin A and the presence of diabetes mellitus were independent coronary risk factors. This is the first report of a potentially deleterious effect of dietary vitamin A in a non-Caucasian population. However it is possible that unidentified residual confounding factors may account for this finding.

Topics: Antioxidants; Ascorbic Acid; Body Mass Index; Cardiovascular Diseases; Carotenoids; Case-Control Studies; Cholesterol; Chromatography, High Pressure Liquid; Diabetes Mellitus; Dietary Fats; Humans; Hypertension; Lipid Peroxidation; Logistic Models; Male; Middle Aged; Multivariate Analysis; Prevalence; Risk Factors; Saudi Arabia; Smoking; Surveys and Questionnaires; Vitamin A; Vitamin E

End organ damage in essential hypertension has been linked to increased oxygen free radical generation, reduced antioxidant defense, and/or attenuation of nitric oxide synthase (NOS) activity. Ascorbic acid (AA), a water-soluble antioxidant, has been reported as a strong defense against free radicals in both aqueous and nonaqueous environment. In this study we examined the hypothesis that antioxidant ascorbic acid may confer protection from increased free radical activity in brain, liver, and blood vessels of spontaneously hypertensive rats (SHR). Male SHRs were divided into groups: SHR + AA (treated with AA, 1 mg/rat/day; for 12 weeks) or SHR (untreated). Wister-Kyoto rats (WKY) served as the control. Mean systolic blood pressure (SBP) in treated and untreated SHR was 145 +/- 7 mmHg and 142 +/- 8 mmHg, respectively. AA treatment prevented the increase in systolic blood pressure in SHR by 37 +/- 1% (p < 0.05). NOS activity in the brain, liver, and blood vessels of WKY rat was 1.82 +/- 0.02, 0.14 +/- 0.003, and 1.54 +/- 0.06 pmol citruline/mg protein, respectively. In SHR, total NOS activity was significantly reduced by 52 +/- 1%, 21 +/- 3%, and 44 +/- 4%, respectively. AA increased NOS activity in brain, liver, and blood vessels of SHR from 0.87 +/-.03, 0.11 +/-.01, and 0.87 +/-.08 pmol citruline/mg protein to 0.93 +/- 0.01, 0.13 +/- 0.001, and 1.11 +/- 0.03 pmol citruline/mg protein (p < 0.05), respectively. Lipid peroxides in the brain, liver, and blood vessels from WKY rats were 0.87 +/- 0.06, 0.11 +/- 0.005, and 0.47 +/- 0.04 nmol MDA equiv/mg protein, respectively. In SHR, lipid peroxides in brain, liver, and blood vessels were significantly increased by 40 +/- 3%, 64 +/- 3%, and 104 +/- 13%, respectively. AA reduced lipid peroxidation in liver and blood vessels by 17 +/- 1% and 34 +/- 3% but not in brain. Plasma lipid peroxides were almost doubled in SHR (p < 0.01) together with a reduction in total antioxidant status (6 +/- 0.1%; p < 0.05), nitrite (53 +/- 2%; p < 0.05) and superoxide dismutase (SOD) activity (36 +/- 2%; p < 0.05). AA treatment reduced plasma lipid peroxide (p < 0.001), and increased TAS (p < 0.001), nitrite (p < 0.001), and SOD activity (p < 0.001). From this study, we conclude that brain, liver, and blood vessels in SHR are susceptible to free radical injury, which reduces the availability of NO either by scavenging it or by reducing its production via inhibiting NOS. In addition, brain, liver, and blood vessels in SHR; may be pr

Topics: Animals; Ascorbic Acid; Blood Vessels; Brain; Free Radical Scavengers; Hypertension; Liver; Male; Nitric Oxide Synthase; Oxidative Stress; Rats

Oxygen-free radicals and other oxygen/nitrogen species are constantly generated in the human body. Most are intercepted by antioxidant defences and perform useful metabolic roles, whereas others escape to damage biomolecules like DNA, lipids and proteins. Garlic has been shown to contain antioxidant phytochemicals that prevent oxidative damage. These include unique water-soluble organosulphur compounds, lipid-soluble organosulphur compounds and flavonoids. Therefore, in the present study, we have tried to explore the antioxidant effect of garlic supplementation on oxidative stress-induced DNA damage, nitric oxide (NO) and superoxide generation and on the total antioxidant status (TAS) in patients of essential hypertension (EH). Twenty patients of EH as diagnosed by JNC VI criteria (Group I) and 20 age and sex-matched normotensive controls (Group II) were enrolled in the study. Both groups were given garlic pearls (GP) in a dose of 250 mg per day for 2 months. Baseline samples were taken at the start of the study, i.e. 0 day, and thereafter 2 months follow-up. 8-Hydroxy-2'-deoxyguanosine (8-OHdG), lipids, lipid peroxidation (MDA), NO and antioxidant vitamins A, E and C were determined. A moderate decline in blood pressure (BP) and a significant reduction in 8-OHdG, NO levels and lipid peroxidation were observed in Group I subjects with GP supplementation. Further, a significant increase in vitamin levels and TAS was also observed in this group as compared to the control subjects. These findings point out the beneficial effects of garlic supplementation in reducing blood pressure and counteracting oxidative stress, and thereby, offering cardioprotection in essential hypertensives.

Topics: 8-Hydroxy-2'-Deoxyguanosine; alpha-Tocopherol; Antihypertensive Agents; Antioxidants; Ascorbic Acid; Blood Pressure; Cell Survival; Clinical Trials as Topic; Deoxyguanosine; Dietary Supplements; DNA Damage; Double-Blind Method; Garlic; Humans; Hypertension; Leukocytes, Mononuclear; Lipid Peroxidation; Lipids; Lipoproteins; Luminescent Measurements; Nitrites; Oxidation-Reduction; Randomized Controlled Trials as Topic; Reactive Oxygen Species; Time Factors; Vitamin A

Insulin decreased A23187-induced hyperpolarization of the erythrocyte membrane in healthy donors. These data indicate that insulin plays a role in the regulation of Ca(2+)-activated potassium channels in human erythrocytes. However, insulin had little effect on hyperpolarization response of cells induced by artificial ascorbate--phenazine methosulfate donor-acceptor system. Addition of insulin to cell suspension from patients with type 2 diabetes mellitus did not modulate hyperpolarization of the erythrocyte membrane induced by A23187 or ascorbate-phenazine methosulfate, which reflects impairment of regulatory mechanisms for Ca(2+)-activated potassium channels in erythrocytes.

Topics: Arteries; Ascorbic Acid; Calcimycin; Calcium; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Case-Control Studies; Diabetes Mellitus, Type 2; Erythrocytes; Female; Humans; Hydrogen-Ion Concentration; Hypertension; Insulin; Ionophores; Male; Methylphenazonium Methosulfate; Oxidation-Reduction

Pre-eclampsia, formerly called pregnancy-induced hypertension, refers to the new onset of hypertension (SBP > or = 140 mmHg or DBP > or = 90 mmHg) and proteinuria (> or = 0.3 g protein in a 24-hour urine specimen or 1+ on dipstick) after 20 weeks of gestation in a previously normotensive women. It is a life-threatening, multi-organ involvement disease and remains the leading cause of maternal death. Its clinical manifestations are the result of generalized vasospasm, activation of the coagulation system, and changes in several humoral and autoregulatory systems related to volume and blood pressure control. Pre-eclampsia is responsible for high perinatal mortality and morbidity rates, primarily due to early termination of pregnancy. Fetus growth restriction, oligohyrdramnios and non-reassuring fetal status are the consequences of chronic placental hypoperfusion. Pre-eclampsia does not appear to accelerate fetal maturation, as once believed. Delivery remains the definitive treatment of choice for pre-eclampsia and should be timely. Cesarean section is not necessary and reserved for the obstetrical indications only. The expectant management may be considered for women remote from term (< 32 to 34 weeks of gestation) with stable and uncomplicated severe disease. The supportive management such as blood pressure control, seizure prevention, and fetal well-being assessment are also important to ensure the satisfactory outcome. To date, no screening test has been proved to be reliable and cost-effective. The prevention of pre-eclampsia with antioxidant therapy (vitamin C, E) has shown promise, but large, randomized trials are needed. Although controversy exists, calcium supplementation has shown no benefit in large trials, and most evidence suggests little or no benefit for low-dose aspirin as prevention in women in the low-risk category.

Topics: Antihypertensive Agents; Antioxidants; Ascorbic Acid; Aspirin; Blood Pressure; Female; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Risk Factors; Vitamin E

Hypertension increases oxidative stress, which can impair myocardial microvascular function and integrity. However, it is yet unclear whether long-term antioxidant intervention in early hypertension would preserve myocardial perfusion and vascular permeability responses to challenge. Pigs were studied after 12 weeks of renovascular hypertension without (n=8) or with daily supplementation of antioxidants (100 IU/kg vitamin E and 1 g vitamin C, n=6), and compared with normal controls (n=7). Myocardial perfusion and microvascular permeability were measured in vivo by electron beam computed tomography before and after 2 cardiac challenges (intravenous adenosine and dobutamine). Basal left ventricular muscle mass was also obtained. Mean arterial pressure was significantly increased in both groups of hypertensive animals (without and with antioxidants, 123+/-9 and 126+/-4 mm Hg, respectively, versus normal, 101+/-4 mm Hg; both P<0.05), but muscle mass was not different among the groups. The impaired myocardial perfusion response to adenosine observed in hypertensives (normal, +51+/-14%; P<0.05 versus baseline; hypertension, +14+/-15%; P=0.3 versus baseline) was preserved in hypertensive pigs that received antioxidants (+44+/-15%; P=0.01 compared with baseline). Long-term antioxidant intervention also preserved subendocardial microvascular permeability responses in hypertension. On the other hand, antioxidant intervention had little effect on the hypertension-induced myocardial vascular dysfunction observed in response to dobutamine. This study demonstrates that the impaired myocardial perfusion and permeability responses to increased cardiac demand in early hypertension are significantly improved by long-term antioxidant intervention. These results support the involvement of oxidative stress in myocardial vascular dysfunction in hypertension and suggest a role for antioxidant strategies to preserve the myocardial microvasculature.

Topics: Animals; Antioxidants; Ascorbic Acid; Capillary Permeability; Coronary Circulation; Coronary Vessels; Female; Hypertension; Microcirculation; Swine; Tomography, X-Ray Computed; Vitamin E

The intake of antioxidants was studied for its ability to predict type 2 diabetes.. A cohort of 2,285 men and 2,019 women 40-69 years of age and free of diabetes at baseline (1967-1972) was studied. Food consumption during the previous year was estimated using a dietary history interview. The intake of vitamin C, four tocopherols, four tocotrienols, and six carotenoids was calculated. During a 23-year follow-up, a total of 164 male and 219 female incident cases occurred.. Vitamin E intake was significantly associated with a reduced risk of type 2 diabetes. The relative risk (RR) of type 2 diabetes between the extreme quartiles of the intake was 0.69 (95% CI 0.51-0.94, P for trend = 0.003). Intakes of alpha-tocopherol, gamma-tocopherol, delta-tocopherol, and beta-tocotrienol were inversely related to a risk of type 2 diabetes. Among single carotenoids, beta-cryptoxanthin intake was significantly associated with a reduced risk of type 2 diabetes (RR 0.58, 95% CI 0.44-0.78, P < 0.001). No association was evident between intake of vitamin C and type 2 diabetes risk.. This study supports the hypothesis that development of type 2 diabetes may be reduced by the intake of antioxidants in the diet.

Topics: Antioxidants; Ascorbic Acid; Body Mass Index; Carotenoids; Cohort Studies; Diabetes Mellitus, Type 2; Diet; Female; Finland; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Risk Factors; Smoking; Vitamin E

Reactive oxygen species play a major role in the development of endothelial dysfunction. It is as yet unspecified whether increased oxidative stress contributes to endothelial dysfunction of the renal vasculature in patients with type 2 diabetes.. Renal haemodynamics were studied in 20 patients with type 2 diabetes and arterial hypertension (age 62 +/- 5 years) and 20 non-diabetic hypertensive patients at baseline and following infusions of the nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA; 4.25 mg/kg); the substrate of nitric oxide synthase, L-arginine (100 mg/kg); and the antioxidant, vitamin C (3 g, co-infused with L-arginine 100 mg/kg).. The response of renal plasma flow (RPF) to L-NMMA (-54 +/- 62 and -45 +/- 42 ml/min/1.73 m(2); P = NS) and L-arginine (+46 +/- 36 and +49 +/- 25 ml/min/1.73 m(2); P = NS) was not different between diabetic and non-diabetic patients. In contrast, vitamin C induced a more pronounced increase in RPF in diabetic than in non-diabetic patients when co-infused with L-arginine (+71+/-47 and +43+/-33 ml/min/1.73 m(2); P<0.05).. The difference in the response of renal perfusion to an antioxidant suggests increased formation of reactive oxygen species and thereby reduced nitric oxide bioavailability in the renal vasculature of patients with type 2 diabetes.

Topics: Aged; Antioxidants; Arginine; Ascorbic Acid; Case-Control Studies; Diabetes Mellitus, Type 2; Drug Combinations; Enzyme Inhibitors; Female; Humans; Hypertension; Infusions, Intravenous; Male; Middle Aged; omega-N-Methylarginine; Renal Circulation

Previous studies have demonstrated that oxidative stress contributes to hypertension and treatments with either antioxidant or immunosuppressive/anti-inflammatory agents improve hypertension in spontaneously hypertensive rats (SHR). The present study was performed to determine if the antihypertensive effects of an antioxidant-rich diet are associated with reduction in the renal immune infiltration. Rats were divided into experimental groups (n=5 each) that were followed 7 months after birth, during which they were fed either a regular or antioxidant-enriched (test) diet as follows: SHR-R group=regular diet; SHR-T group=test diet throughout the experiment; SHR-S group=test diet for 4 months switched to regular diet thereafter; WKY group=control rats given regular diet. The SHR-T rats showed a significant reduction in systolic blood pressure (mm Hg): SHR-T=179.6+/-12.9 versus SHR-R=207.5+/-9.6 (P<0.001) and plasma hydrogen peroxide concentration (SHR-T=15+/-4 micro mol/L versus 34+/-9 in SHR-R rats). This was accompanied by significant reductions of renal tissue nitrotyrosine abundance, tubulointerstitial infiltration (cells/mm(2)) of lymphocytes (SHR-T=18+/-3 versus SHR-R=30+/-4, P<0.001), macrophages (SHR-T= 17+/-3 versus SHR-R=22+/-3), and angiotensin II-positive cells (SHR-T= 17+/-2 versus SHR-R=25+/-5, P<0.01). Results in the SHR-S group were intermediate between the SHR-R and SHR-T groups. The intensity of the infiltration of lymphocytes, macrophages, and angiotensin II-positive cells significantly correlated with systolic blood pressure. Thus, the present study demonstrates that an antioxidant-enriched diet reduces the renal interstitial inflammation and improves hypertension in SHR. These findings point to interrelation between oxidative stress and inflammatory reactivity in the pathogenesis of hypertension.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Diet; Female; Hydrogen Peroxide; Hypertension; Kidney; Kidney Glomerulus; Lymphocytes; Macrophages; Male; Malondialdehyde; Pregnancy; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vitamin E

Antioxidant vitamins C and E have protective properties in genetic hypertension associated with enhanced oxidative stress. This study investigated whether vitamins C and/or E modulate vascular function by regulating enzymatic activities of endothelial nitric oxide synthase (eNOS) and NAD(P)H oxidase using thoracic aortas of 20- to 22-week-old male spontaneously hypertensive rats (SHR) and their matched normotensive counterparts, Wistar-Kyoto rats (WKY). SHR aortas had impaired relaxant responses to acetylcholine but not to sodium nitroprusside, despite an approximately 2-fold increase in eNOS activity and NO release. The levels of superoxide anion (O2-), a potent NO scavenger, and NAD(P)H oxidase activity were also 2-fold higher in SHR aortas. Mechanical but not pharmacological inactivation of endothelium (by rubbing and 100 micromol/L L-NAME, respectively) significantly abrogated O2- in both strains. Treatments of SHR aortas with NAD(P)H oxidase inhibitors, namely diphenyleneiodinium and apocynin, significantly diminished O2- production. The incubation of SHR aortas with different concentrations of vitamin C (10 to 100 micromol/L) and specifically with high concentrations of vitamin E (100 micromol/L) improved endothelial function, reduced superoxide production as well as NAD(P)H oxidase activity, and increased eNOS activity and NO generation in SHR aortas to the levels observed in vitamin C- and E-treated WKY aortas. Our results reveal endothelial NAD(P)H oxidase as the major source of vascular O2- in SHR and also show that vitamins C and E are critical in normalizing genetic endothelial dysfunction through regulation of eNOS and NAD(P)H oxidase activities.

Topics: Animals; Antioxidants; Aorta, Thoracic; Ascorbic Acid; Culture Techniques; Endothelium, Vascular; Hypertension; Male; NADPH Oxidases; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Superoxides; Vasodilation; Vitamin E; Vitamins

Blood pressure (BP) increases in postmenopausal women. The mechanisms responsible are unknown. The present study was performed to characterize a model of postmenopausal hypertension in the rat and to determine the role that oxidative stress may play in mediating the postmenopausal hypertension. Spontaneously hypertensive rats were ovariectomized (ovx) or left intact (PMR) at 8 months and were aged to 18 months. These animals were compared with young females (YF; 4 or 8 months of age) and old males (18 months) for some measurements. Estradiol levels were decreased in PMR rats to levels not different from YF rats in proestrous or from old males. BP increased progressively with age in PMR rats but not in ovx or male rats, such that the gender difference in hypertension disappeared by 18 months. Glomerular filtration rate was lower in ovx and PMR rats than in YF rats. Renal plasma flow and renal vascular resistance were similar between YF and ovx rats, but lower and higher, respectively, in PMR rats. Serum testosterone increased by 60% in ovx rats and 400% in PMR rats compared with YF rats. Plasma renin activity also increased in PMR rats but not in ovx rats. Chronic treatment (for 8 months beginning at 8 months of age) of PMR rats with vitamins E and C, but not tempol, resulted in a significant reduction in BP and excretion of F2-isoprostanes. In contrast, tempol, but not vitamins E and C, reduced BP in old males. These data suggest that the PMR rats, but not ovx rats, may be a suitable model for the study of postmenopausal hypertension, and that oxidative stress plays a role in the increased BP.

Topics: Age Factors; Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Cyclic N-Oxides; Disease Models, Animal; Estradiol; Female; Hemodynamics; Hypertension; Kidney; Male; Ovariectomy; Oxidative Stress; Postmenopause; Rats; Rats, Inbred SHR; Spin Labels; Vaginal Smears; Vitamin E

Our objective was to prospectively examine the relation between vitamin C intake and risk of coronary heart disease (CHD) in women.. Results from prospective investigations of the relation between vitamin C intake and risk of CHD have been inconsistent. The lack of clear evidence for a protective association despite a plausible mechanism indicates the need to evaluate further the association between vitamin C intake and risk of CHD.. In 1980, 85,118 female nurses completed a detailed semiquantitative food-frequency questionnaire that assessed their consumption of vitamin C and other nutrients. Nurses were followed up for 16 years for the development of incident CHD (nonfatal myocardial infarction and fatal CHD).. During 16 years of follow-up (1,240,566 person-years), we identified 1,356 incident cases of CHD. After adjustment for age, smoking, and a variety of other coronary risk factors, we observed a modest significant inverse association between total intake of vitamin C and risk of CHD (relative risk [RR] = 0.73; 95% confidence interval [CI] 0.57 to 0.94). Among women who did not use vitamin C supplements or multivitamins, the association between intake of vitamin C from diet alone and incidence of CHD was weak and not significant (RR = 0.86; 95% CI 0.59 to 1.26). In multivariate models adjusting for age, smoking, and a variety of other coronary risk factors, vitamin C supplement use was associated with a significantly lower risk of CHD (RR = 0.72; 95% CI 0.61 to 0.86).. Users of vitamin C supplements appear to be at lower risk for CHD.

Topics: Adult; Age Factors; Antioxidants; Ascorbic Acid; Chemoprevention; Coronary Disease; Diabetes Complications; Dietary Supplements; Female; Humans; Hypercholesterolemia; Hypertension; Incidence; Life Style; Logistic Models; Middle Aged; Multivariate Analysis; Nutrition Surveys; Proportional Hazards Models; Prospective Studies; Risk Factors; Smoking; Surveys and Questionnaires; United States; Women's Health

SHR-od is a novel strain of rat that spontaneously develops hypertension and has a defect of ascorbic acid (AsA) biosynthesis. The osteogenic disorder Shionogi (ODS) rat is normotensive and also unable to synthesize AsA. To investigate whether or not genetic hypertension affects AsA metabolism, we compared the AsA metabolisms of SHR-od and ODS rats. In this study, a physiological dose of AsA equivalent to the AsA requirement in ODS rats was administered to rats intraperitoneally (i.p. group) or orally (oral group). We measured AsA concentrations in the serum, liver, kidney, adrenal glands, and spleen, and the amount of AsA excreted into the urine. At 25 wk of age (hypertensive status), the AsA concentrations of all tissues tested were significantly lower in SHR-od than in ODS rats in both the i.p. and oral groups. In the i.p. group, the amount of urinary AsA in SHR-od was also lower than that in ODS rats. At 4 wk of age (before the onset of hypertension), liver and spleen AsA concentrations in SHR-od were lower than those in ODS rats in both the i.p. and oral groups. Urinary AsA excretion from SHR-od was not different between the two groups. Our data suggest that the requirement for AsA in SHR-od is increased to maintain tissue AsA concentrations equivalent to those in ODS rats, and that a larger part of the AsA administered to rats in this study is degraded in SHR-od as compared to ODS rats.

Topics: Adrenal Glands; Animals; Ascorbic Acid; Hypertension; Kidney; Liver; Male; Osteogenesis; Rats; Rats, Inbred SHR; Scurvy; Spleen; Thiobarbituric Acid Reactive Substances

Epidemiological studies suggest that intrauterine undernutrition plays an important role in the development of arterial hypertension in adulthood. Ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) have antioxidant properties that could improve redox-sensitive vascular changes associated with hypertension. The authors determined whether vitamins C and E treatments ameliorate the hypertension and vascular function in male rats submitted to intrauterine undernutrition. Pregnant Wistar rats were fed either normal or 50% of the normal intake diets during the whole gestational period. At 14 weeks of age, male offspring of nutritionally restricted dams were divided into 3 subgroups: vehicle-treated (vehicle for 15 days, by gastric gavage, n = 9), vitamin C-treated (ascorbic acid, 150 mg/Kg/d for 15 days, by gastric gavage, n = 15) and vitamin E-treated (alpha-tocopherol, 350 mg/kg per day for 15 days, by gastric gavage, n = 15). Systolic blood pressure was determined before and after antioxidant treatments by the tail-cuff method. At 16 weeks of age, the rats were used for the study of microvascular reactivity and intravital fluorescence microscopy. Intrauterine undernutrition induced hypertension, and vitamins C or E treatments reduced the blood pressure levels. The decreased acetylcholine and bradykinin-induced vasodilation was restored in the vitamin-treated rats. These effects were associated with decreased vascular superoxide anion concentration. The results show that vitamins C and E reduce oxidative stress and high blood pressure levels, and improve vascular function in intrauterine-undernourished rats.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Endothelium, Vascular; Female; Hypertension; Male; Placental Insufficiency; Pregnancy; Rats; Superoxides; Vitamin E

Chronic exposure to lead results in sustained hypertension in humans and experimental animals. We investigated the possible role of reactive oxygen species (ROS) and their impact on DNA damage in lead-induced hypertension. Further the effect of short-term supplementation of vitamin C is also demonstrated.. Male Wistar rats were treated with either lead acetate (100 ppm) alone or lead acetate plus vitamin C (20 mg/rat/day). The control rats were fed regular rat chow. Blood pressure, antioxidants, total antioxidant status as measured by ferric-reducing antioxidant power, nitric oxide (NO) metabolites, malondialdehyde (MDA) and 8-hydroxy 2-deoxyguanosine were determined after 0, 1, 2 and 3 months.. The lead-exposed group showed a significant rise in blood pressure, lipid peroxidation (MDA) and a substantial oxidative damage to the DNA. A significant fall in NO metabolites, total antioxidant levels and ferric-reducing antioxidant power was also observed in this group. Concomitant administration of vitamin C ameliorated hypertension, normalized NO levels and abrogated lipid peroxidation. Also, it completely prevented oxidative damage to the DNA.. These findings point to enhanced ROS-mediated inactivation and sequestration of NO which can potentially contribute to hypertension, lipid peroxidation, reduced antioxidant status and oxidative DNA damage. The beneficial effects of vitamin C on these parameters support the role of increased ROS activity in the pathogenesis of these abnormalities in this model.

Topics: Animals; Antioxidants; Ascorbic Acid; Deoxyadenosines; Dietary Supplements; Disease Models, Animal; DNA Damage; Hypertension; Lead Poisoning; Lipid Peroxidation; Male; Malondialdehyde; Nitric Oxide; Organometallic Compounds; Oxidation-Reduction; Random Allocation; Rats; Rats, Inbred WKY; Reactive Oxygen Species; Time Factors

Coupling factor 6 is an endogenous inhibitor of prostacyclin synthesis and might function as an endogenous vasoconstrictor in the fashion of a circulating hormone in rats. We investigated the role of coupling factor 6 in human hypertension.. The patients with essential hypertension (EH) (n = 30) received a series of normal salt diet (12 g salt/day) for 3 days, low salt diet (2 g salt/day) for 7 days, and high salt diet (20-23 g salt/day) for 7 days. Normotensive control subjects (n = 27) received normal and low salt diets. The plasma level of coupling factor 6, measured by radioimmunoassay, during normal salt diet was higher in patients with EH than in normotensive subjects (17.6 +/- 1.7 versus 12.8 +/- 0.5 ng/ml, P < 0.01). Whereas the plasma level of coupling factor 6 was unchanged after salt restriction in normotensive subjects, it was decreased after salt restriction (from 12 g/day to 2 g/day) and was increased after salt loading (from 2 g/day to 20-23 g/day) in patients with EH. This increase in plasma level of coupling factor 6 was abolished by oral administration of ascorbic acid, but the level of blood pressure was unaffected. The percentage changes in plasma coupling factor 6 level after salt restriction and loading were positively correlated with those in mean blood pressure (r = 0.57, P < 0.01), and negatively correlated with those in plasma nitric oxide level (r = -0.51, P < 0.05).. These indicate that circulating coupling factor 6 is elevated in human hypertension and modulated by salt intake presumably via reactive oxygen species.

Topics: Antioxidants; Ascorbic Acid; Biomarkers; Blood Pressure; Diet, Sodium-Restricted; Dinoprost; Endothelial Cells; Female; Humans; Hypertension; Male; Middle Aged; Mitochondrial Proton-Translocating ATPases; Nitrates; Nitrites; Norepinephrine; Oxidative Phosphorylation Coupling Factors; Reactive Oxygen Species; Renin; Sodium, Dietary; Statistics as Topic

By breeding and feeding salt to spontaneously hypertensive rats (SHR) continuously over a long period (until 60 wk old), rats with systolic blood pressures (SBP) of over 270 mmHg were prepared. It was studied whether or not supplying large amounts of vitamin C (200 mg/rat/d) over this period might bring any beneficial effect to blood pressure. Moreover, physico-chemical studies were performed to measure the components and enzymes in the blood and urine at 53 and 60 wk-old, and biochemical studies on vitamin C were also carried out in this experiment. Male (14 rats: 7 wk-old, 100-105 g) and female (15 rats: 7 wk-old, 95-100 g) SHR were divided into three groups and bred continuously for 53 wk. The A group rats were given salt (2.5 g/100 g of diet), the B group rats were given salt and vitamin C (500 mg/100 mL of drinking water), and the C group rats were controls. The results showed almost the same tendencies between male and female rats. The body weights of the SHR in groups A and B were slightly lower than group C. The amount of food intake in groups A and B was almost the same as group C. The amount of water intake was, in the order from highest to lowest, group A, B and C. The SBP of group A rats exhibited the highest value among the three groups. The SBP of group B rats given vitamin C simultaneously with the salt resulted in a low blood pressure level close to that of the controls (group C). Furthermore, the DBP (diastolic blood pressure) also reflected the antihypertensive effect of vitamin C as well. The heartbeat of the rats was highest in group A, and was comparable to the value in the rats receiving vitamin C simultaneously with salt. For the tests on occult blood and protein in the urine, group A rats showed strong positive reactions, whereas the group B and C rats had decreased results for both tests. The organ weights of the liver, stomach, spleen, adrenal gland and kidneys per 100 g rat body weight were not different among the three groups. The values for the bilirubin content, and the enzyme activities of ALT and AST in the blood showed to be the highest in the male rats of group A. The values from the group B rats decreased near to the normal value like the control group. Vitamin C was found to decrease the blood pressure in SHR, and also to work effectively to protect liver and kidney functions even under the condition of very high blood pressure, as high as 250 mmHg.

Topics: Alanine Transaminase; Animals; Ascorbic Acid; Aspartate Aminotransferases; Body Weight; Drinking; Eating; Female; Hematuria; Hypertension; Male; Organ Size; Proteinuria; Rats; Rats, Inbred SHR; Sodium Chloride, Dietary

Many peroxidation processes taking place in organisms both in normal and pathological conditions are initiated among others by free radicals. Organisms developed many protective mechanisms to fight with detrimental effects of free radical activity. The aim of the study was to evaluate antioxidant protective barrier by determination of concentrations of some non-enzymatic parameters such as L-ascorbic acid and tocopherol in blood plasma, and to correlate assessed values with basic lipoprotein parameters. The study was carried out in 144 pregnant women in the second and third trimester. The subject were divided into four groups: diabetic pregnancy, pregnancy induced hypertension, diabetic pregnancy with hypertension, and healthy pregnant women. The study results show that pregnancy induced hypertension, diabetic pregnancy and diabetic pregnancy with hypertension are the factors which disturb lipoprotein metabolism and may cause atherosclerotic changes. Higher concentrations of alpha-tocopherol and L-ascorbic acid in plasma in diabetic pregnancy with hypertension may be an important factor which adopts woman's organism to oxidation stress in complicated pregnancy.

Topics: Antioxidants; Ascorbic Acid; Biomarkers; Female; Humans; Hypertension; Lipoproteins; Oxidative Stress; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Tocopherols

The effects of a vitamin C supplemented diet on blood pressure, body and liver weights, liver antioxidant status, iron and copper levels were investigated in DOCA-salt treated and untreated Sprague-Dawley (SD) male rats after 8 weeks of treatment. Vitamin C supplementation had no effect on blood pressure in SD rats but induced a significant decrease in blood pressure in DOCA-salt treated rats, the decrease being more efficient at 50 mg/kg of vitamin C than at 500 mg/kg. Hepatic lipid peroxidation and iron levels were significantly increased in DOCA-salt hypertensive rats whereas total hepatic antioxidant capacity (HAC), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were decreased. Vitamin C supplementation did not affect the overall antioxidant defences of control SD rat livers. In contrast, vitamin C supplementation accentuated the DOCA-salt induced accumulation of liver iron and lipid peroxidation. This occurred without any notable aggravation in the antioxidant deficiency of vitamin C supplemented DOCA-salt treated rat livers. Our data suggest that DOCA-salt treatment induces an accumulation of iron in rat livers which is responsible for the prooxidant effect of vitamin C. The normalization of blood pressure in DOCA-salt treated rats by vitamin C supplementation appears thus independent from liver antioxidant status.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Catalase; Copper; Desoxycorticosterone; Dietary Supplements; Free Radical Scavengers; Glutathione Peroxidase; Hypertension; Iron; Liver; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley

Topics: Antioxidants; Ascorbic Acid; Blood Pressure; Confounding Factors, Epidemiologic; Diabetes Complications; Diet; Humans; Hypertension; Potassium, Dietary; Randomized Controlled Trials as Topic; Reproducibility of Results; Research Design; Stomach Diseases; Time; Treatment Outcome

Serum vitamin C has been inversely associated with blood pressure in several epidemiologic studies, but little is known about effect of other antioxidant vitamins. We examined the relation between serum vitamins A, C, and E, alpha-carotene, and beta-carotene levels and blood pressure among 15 317 men and women > or =20 years of age who participated in the Third National Health and Nutrition Examination Survey. Blood pressure was characterized as the average of 6 measurements obtained over 2 visits by trained observers and hypertension was defined as blood pressure > or =140/90 mm Hg and/or taking antihypertensive medications. In multivariate models, a 1 SD difference in vitamin A (16.2 microg/dL) and vitamin E (20.4 microg/dL) was associated with a 43% (OR, 1.43; 95% CI, 1.34 to 1.53) and 18% (OR, 1.18; 95% CI, 1.09 to 1.27) higher odds of hypertension, respectively. A 1 SD difference in alpha-carotene (0.47 micro g/dL) and beta-carotene (496 microg/dL) was associated with a 16% (OR, 0.84; 95% CI, 0.76 to 0.94) and 11% (OR, 0.89; 95% CI, 0.82 to 0.97) lower odds of hypertension, respectively. In addition, serum vitamins A and E were positively and significantly associated with both systolic and diastolic blood pressure, whereas alpha-carotene and beta-carotene were inversely and significantly associated with systolic and vitamin C associated with diastolic blood pressure in multivariate linear regression analyses. These findings indicate that antioxidant vitamins may be important in the underlying cause and prevention of hypertension. Further studies in this important area are warranted.

Topics: Adult; Antioxidants; Ascorbic Acid; beta Carotene; Blood Pressure; Carotenoids; Diastole; Female; Humans; Hypertension; Linear Models; Logistic Models; Male; Middle Aged; Multivariate Analysis; Nutrition Surveys; Odds Ratio; Racial Groups; Systole; United States; Vitamin A; Vitamin E; Vitamins

In fructose-induced hypertension in Wistar-Kyoto (WKY) rats, excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing cytosolic free calcium and blood pressure. The thiol compound N-acetyl cysteine prevents fructose-induced hypertension by binding excess endogenous aldehydes and normalizing membrane Ca2+ channels and cytosolic free calcium. The aim of the present study was to investigate whether dietary supplementation of vitamin E and vitamin C which are known to increase tissue glutathione, a storage form of cysteine, prevents this hypertension and its associated biochemical and histopathological changes. Starting at 7 weeks of age, animals were divided into four groups of six animals each and treated as follows: control group, normal diet and normal drinking water; fructose group, normal diet and 4% fructose in drinking water; fructose + vitamin E group, diet supplemented with vitamin E (34 mg/ kg feed) and 4% fructose in drinking water; fructose + vitamin C group, diet supplemented with vitamin C (1,000 mg/kg feed) and 4% fructose in drinking water. At 14 weeks, systolic blood pressure, platelet [Ca2+]i and kidney and aortic aldehyde conjugates were significantly higher in the fructose group. These animals also displayed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin E and C supplementation in fructose-treated WKY rats prevented the increase in systolic blood pressure by normalizing cytosolic [Ca2+]i and kidney and aortic aldehyde conjugates and preventing adverse renal vascular changes.

Topics: Animals; Ascorbic Acid; Blood Platelets; Body Weight; Calcium; Drinking Behavior; Feeding Behavior; Fructose; Hypertension; Organ Size; Rats; Rats, Inbred WKY; Vitamin E

The present study was undertaken to investigate the effect of vitamin C treatment on blood pressure and vascular reactivity in salt-induced hypertension. Male Sprague-Dawley rats were fed a normal rat diet, a high-sodium (8% NaCl) diet, a normal rat diet plus vitamin C treament (100 mg x kg(-1) x day(-1)), or a high-sodium diet plus vitamin C treatment for 6 weeks. Salt loading significantly increased blood pressure, which was attenuated by vitamin C treatment. Aortic rings from the different groups were suspended for isometric-tension recording. The contractile response to noradrenaline was significantly increased in the salt-loaded rats. Vitamin C reduced the sensitivity of aortic rings to noradrenaline in rats on normal and high-sodium diets. In noradrenaline-precontracted rings, the relaxation response to acetylcholine, which was attenuated in the salt-loaded rats, was restored by vitamin C treatment. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) abolished the enhanced response to acetylcholine caused by vitamin C. The results suggest that the antihypertensive effect of vitamin C is associated with a reduction in vascular sensitivity to noradrenaline and enhancement of endothelium-dependent relaxation due to increased nitric oxide bioavailability.

Topics: Animals; Ascorbic Acid; Blood Pressure; Dose-Response Relationship, Drug; Hypertension; In Vitro Techniques; Male; Rats; Rats, Sprague-Dawley; Sodium Chloride, Dietary; Vasoconstriction; Vasodilation

Although in hypertension a defect in stimulated nitric oxide (NO) is well established, little is known about basal NO levels. Thus, we measured directly in vessels from normotensive [Wistar-Kyoto (WKY)] rats and spontaneously hypertensive rats (SHR) both basal and stimulated NO production using a novel technique [4,5-diaminofluorescein (DAF-2) fluorescence].. Isolated vessels were exposed to the fluorescent probe DAF-2. After the technique was validated with increasing doses of acetylcholine in the presence and absence of NG-nitro-L-arginine methyl ester (l-NAME), we measured NO production in vessels from WKY rats and SHR in the same experimental setting. Finally, to explore the impact of reactive oxygen species (ROS) on NO release, we analysed the effect of an antioxidant, such as ascorbic acid, on basal and stimulated NO in aortic rings of WKY rats and SHR.. Aortic rings from SHR exhibited a higher basal NO production and a lower responsiveness to agonist-induced NO release as compared with those observed in WKY rats. Also in resistance vessels such as mesenteric arteries, basal NO production was higher in hypertension. In hypertensive rats, ascorbic acid was able to further increase basal NO release and recovered the impaired stimulated NO production, whereas no effect was detected in normotensive rats.. Our data reveal an increased basal NO availability in hypertension despite the increased production of ROS, suggesting a greater complexity in hypertensive endothelial dysfunction when the analysis is focused on direct NO measurement.

Topics: Acetylcholine; Animals; Antioxidants; Aorta; Ascorbic Acid; Enzyme Inhibitors; Fluorescein; Hypertension; In Vitro Techniques; Indicators and Reagents; Male; Mesenteric Arteries; NG-Nitroarginine Methyl Ester; Nitric Oxide; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reactive Oxygen Species

The present study was designed to evaluate the possible antioxidant effect of pergolide, a DA-2 receptor agonist, in deoxycorticosterone acetate (DOCA)-salt hypertension and its role in endogenous endothelin-1 (ET- 1) production and organ hypertrophy. Male Sprague-Dawley rats were uninephrectomized (UNx) or uninephrectomized, and received subcutaneous implants of DOCA and drank 1% sodium chloride (DOCA). DOCA rats were treated daily for 3 weeks with pergolide (1 mg/kg, i.p.) or vitamin C (1 mg/rat, orally). DOCA-salt treatment increased systolic blood pressure (SBP) in UNx rats by 45 +/- 2 mmHg from 117 +/- 5 to 162 +/- 10 mmHg (p < 0.05), an effect blunted by pergolide and vitamin C. Superoxide generation was not increased in DOCA rats; however, both pergolide and vitamin C significantly reduced superoxide generation by 49 +/- 7% and 52 +/- 13%, respectively (p < 0.05). Plasma ET-1 levels increased twofold in UNx rats but was reduced to 42 +/- 7% (p < 0.05) in DOCA compared to UNx rats. Pergolide and vitamin C reduced plasma ET-1 levels further by 43 +/-10% (p < 0.05) and 46 +/- 8% (p < 0.05), respectively. Pergolide increased urinary Na+ excretion but did not alter urinary protein excretion or the left ventricular and aortic hypertrophy in DOCA rats. These data suggest that the reduction of SBP by pergolide in DOCA-salt hypertension may be attributed to its natriuretic ability, not its ability to reduce superoxide generation or ET- 1 production.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Desoxycorticosterone; Dopamine Agonists; Endothelin-1; Hypertension; Kidney; Male; Natriuresis; Pergolide; Rats; Rats, Sprague-Dawley; Superoxides

There are no prospective studies to determine whether plasma vitamin C modifies the risk of stroke among hypertensive and overweight individuals. We sought to examine whether plasma vitamin C modifies the association between overweight and hypertension and the risk of stroke in middle-aged men from eastern Finland.. We conducted a 10.4-year prospective population-based cohort study of 2419 randomly selected middle-aged men (42 to 60 years) with no history of stroke at baseline examination. A total of 120 men developed a stroke, of which 96 were ischemic and 24 hemorrhagic strokes.. Men with the lowest levels of plasma vitamin C (<28.4 micromol/L, lowest quarter) had a 2.4-fold (95% CI, 1.4 to 4.3; P=0.002) risk of any stroke compared with men with highest levels of plasma vitamin C (>64.96 micromol/L, highest quarter) after adjustment for age and examination months. An additional adjustment for body mass index, systolic blood pressure, smoking, alcohol consumption, serum total cholesterol, diabetes, and exercise-induced myocardial ischemia attenuated the association marginally (relative risk, 2.1; 95% CI, 1.2 to 3.8; P=0.01). Adjustment for prevalent coronary heart disease and atrial fibrillation did not attenuate the association any further. Furthermore, hypertensive men with the lowest vitamin C levels (<28.4 micromol/L) had a 2.6-fold risk (95% CI, 1.52 to 4.48; P<0.001), and overweight men (> or =25 kg/m2) with low plasma vitamin C had a 2.7-fold risk (95% CI, 1.48 to 4.90; P=0.001) for any stroke after adjustment for age, examination months, and other risk factors.. Low plasma vitamin C was associated with increased risk of stroke, especially among hypertensive and overweight men.

Topics: Adult; Ascorbic Acid; Body Mass Index; Brain Ischemia; Cerebral Hemorrhage; Cohort Studies; Demography; Finland; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Obesity; Prospective Studies; Risk; Risk Assessment; Risk Factors; Stroke

Essential hypertension is associated with impaired endothelium-dependent vasodilation caused by oxygen free radical-induced nitric oxide (NO) breakdown. Because calcium antagonists can improve endothelial function in patients with essential hypertension, in this study we tested the hypothesis that this beneficial effect could be related to restoration of NO availability by antioxidant properties. In 15 healthy subjects and 15 hypertensive patients, we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (ACh; 0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute), an endothelium-dependent vasodilator in basal conditions, during infusion of N:(G)-monomethyl-L-arginine (L-NMMA, 100 microg/100 mL forearm tissue per minute), an NO-synthase inhibitor, vitamin C (8 mg/100 mL forearm tissue per minute), and finally, simultaneous infusion of L-NMMA and vitamin C. The response to sodium nitroprusside (SNP; 1, 2, and 4 microg/100 mL forearm tissue per minute) was also evaluated. In control subjects, vasodilation to ACh was inhibited by L-NMMA and not changed by vitamin C. In hypertensive patients, vasodilation to ACh was blunted as compared with control subjects and resistant to L-NMMA. Vitamin C, which decreased plasma isoprostanes and increased plasma antioxidant capacity, increased the response to ACh and restored the inhibiting effect of L-NMMA. In hypertensive patients, the study was repeated after 3-month treatment with nifedipine gastrointestinal therapeutic system (30 to 60 mg/daily). Nifedipine treatment decreased circulating plasma lipoperoxides and isoprostanes and increased plasma antioxidant capacity. Moreover, nifedipine increased the vasodilation to ACh but not to SNP and restored the inhibiting effect of L-NMMA on ACh-induced vasodilation, whereas vitamin C no longer exerted its facilitating activity. These results indicate that nifedipine increases endothelium-dependent vasodilation by restoring NO availability, an effect probably determined by antioxidant activity.

Topics: Acetylcholine; Antioxidants; Ascorbic Acid; Blood Pressure; Calcium Channel Blockers; Endothelium, Vascular; Enzyme Inhibitors; Female; Forearm; Heart Rate; Humans; Hypertension; Male; Middle Aged; Nifedipine; Nitric Oxide; Nitric Oxide Synthase; omega-N-Methylarginine; Oxidative Stress; Regional Blood Flow; Time Factors; Vasodilation

Topics: Ascorbic Acid; Female; Humans; Hypertension; Male; Nutrition Policy; Tunica Intima; Tunica Media

Peripheral arterial disease (PAD) is a severe atherosclerotic condition frequently accompanied by inflammation and oxidative stress. We hypothesized that vitamin C antioxidant levels might be low in PAD and are related to inflammation and disease severity.. We investigated vitamin C (L-ascorbic acid) levels in 85 PAD patients, 106 hypertensives without PAD, and 113 healthy subjects. Serum L-ascorbic acid concentrations were low among PAD patients (median, 27.8 micromol/L) despite comparable smoking status and dietary intake with the other groups (P<0.0001). Subclinical vitamin C deficiency (<11.4 micromol/L), confirmed by low serum alkaline phosphatase activity, was found in 14% of the PAD patients but not in the other groups. Serum C-reactive protein (CRP) concentrations were significantly higher in PAD patients (P<0.0001) and negatively correlated with L-ascorbic acid levels (r=-0.742, P<0.0001). In stepwise multivariate analysis, low L-ascorbic acid concentration in PAD patients was associated with high CRP level (P=0.0001), smoking (P=0.0009), and shorter absolute claudication distance on a standardized graded treadmill test (P=0.029).. Vitamin C concentrations are lower in intermittent claudicant patients in association with higher CRP levels and severity of PAD. Future studies attempting to relate vitamin C levels to disease occurrence should include in their analysis an inflammatory marker such as CRP.

Topics: Aged; Arteriosclerosis; Ascorbic Acid; Aspirin; C-Reactive Protein; Female; Fibrinogen; Humans; Hypertension; Inflammation; Lipids; Male; Middle Aged; Multivariate Analysis; Peripheral Vascular Diseases; Severity of Illness Index; Smoking

In spontaneously hypertensive rats (SHRs) excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing cytosolic free calcium and blood pressure. The thiol compound, N-acetyl cysteine, normalizes elevated blood pressure in SHRs by binding excess endogenous aldehydes. Vitamin C can increase tissue cysteine and glutathione levels. The aim of the present study was to investigate whether a dietary supplementation of vitamin C can lower tissue aldehydes and blood pressure and normalize associated biochemical and histopathological changes in SHRs. Starting at 12 weeks of age, animals were divided into 3 groups of 6 animals each. Animals in the WKY-control group and SHR-control group were given a normal diet and the SHR-vitamin C group a diet supplemented with vitamin C (1000 mg/kg feed) for the next 9 weeks. After nine weeks, systolic blood pressure, platelet [Ca2+]i, plasma insulin and liver, kidney and aortic aldehyde conjugates were significantly higher in SHR controls as compared to WKY controls and the SHR-vitamin C group. SHR-controls also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin C supplementation in SHRs lowered the systolic blood pressure, tissue aldehyde conjugates and attenuated adverse renal vascular changes.

Topics: Aldehydes; Animals; Antioxidants; Ascorbic Acid; Blood Platelets; Blood Pressure; Body Weight; Calcium; Dietary Supplements; Drinking; Eating; Hyperplasia; Hypertension; Liver; Organ Size; Rats; Rats, Inbred SHR; Rats, Inbred WKY

Biologically active additives in integrated therapy of patients with cardiovascular diseases against a background body overweight. The influence of antiaterosclerotic diet with including some biologically active additives, which contain vitamins C, E, B2, B6, beta-carotene, Zn, Mg, Na, K, Ca, I was studied in 91 patients with ischemic heart disease, hypertension disease. The usage of biologically active additives during 4 weeks has promoted positive changes of clinical symptoms of diseases against a background of lowering of serum cholesterol, triglycerides and increasing of vitamins A, E, C, B2, B6.

Topics: Adult; Antioxidants; Ascorbic Acid; beta Carotene; Blood Glucose; Cholesterol; Dietary Supplements; Humans; Hypertension; Lipid Peroxidation; Middle Aged; Myocardial Ischemia; Pyridoxine; Riboflavin; Time Factors; Triglycerides; Vitamin E; Vitamins

We conducted a case-control study nested within a prospective cohort study of 13,979 residents of Leisure World Laguna Hills, a retirement community in southern California, for etiologic clues for Parkinson's disease (PD). Between 1981 (when first mailed a health survey) and 1998, we identified 395 PD cases from death certificates, hospital discharge diagnoses and a 1992 follow-up questionnaire. Six controls were individually matched on sex, birth date (+/-2 years), vital status and, if dead, death date (+/-1 year) to each case. Baseline characteristics of the 395 cases and 2,320 controls were analyzed as potential PD risk factors. The risk of PD was significantly reduced among smokers, hypertensives, coffee drinkers and alcohol consumers, and significantly increased among those with 3 or more children and with a high intake of total vitamin A and dietary vitamin C. The multivariate odds ratios (95% confidence intervals) were 0.42 (0.22-0.80) for current cigarette smokers of 1+ pack/day, 0.62 (0.48-0.80) for current users of hypertensive medication, 0.71 (0.52-0.95) for coffee drinkers of 2+ cups/day and 0.77 (0.58-1.03) for drinkers of 2+ alcoholic drinks/day. Risk increased with increasing number of children (1.25 for 1, 1.34 for 2 and 1.90 for 3+ children; p for trend = 0.0003). The increased risks among individuals in the highest third of total vitamin A intake and of dietary vitamin C intake were no longer statistically significant after adjusting for the other variables. These findings suggest several environmental factors that may be related to the development of PD and support a multifactorial etiology.

Topics: Adult; Aged; Aged, 80 and over; Alcoholism; Ascorbic Acid; Caffeine; California; Case-Control Studies; Catchment Area, Health; Cohort Studies; Female; Humans; Hypertension; Male; Middle Aged; Parkinson Disease; Prospective Studies; Risk Factors; Smoking; Vitamin A

Age-related endothelial dysfunction could be caused by an alteration in the L-arginine-NO system and the production of oxidative stress in both normotensive and hypertensive individuals. In 47 normotensive subjects and 49 patients with essential hypertension, we evaluated forearm blood flow (by strain-gauge plethysmography) modifications induced by intrabrachial sodium nitroprusside (1, 2, and 4 microg/100 mL per minute) and acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute), an endothelium-independent vasodilator and an endothelium-dependent vasodilator, respectively. Acetylcholine was repeated in the presence of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 100 microg/100 mL per minute), the antioxidant vitamin C (8 mg/100 mL per minute), or both. Vasodilation to acetylcholine, but not to sodium nitroprusside, was lower (P<0.01) in hypertensive patients compared with control subjects. Moreover, in both groups, endothelium-dependent vasodilation declined with aging. In normotensive subjects, the inhibiting effect of L-NMMA on response to acetylcholine decreased in parallel with advancing age, whereas vitamin C increased vasodilation to acetylcholine in only the oldest group (age >60 years). In young hypertensive patients (age <30 years), vasodilation to acetylcholine was sensitive to L-NMMA, whereas in hypertensive patients age >30 years, vitamin C enhanced endothelium-dependent vasodilation and restored the inhibiting effect of L-NMMA on response to acetylcholine. In normotensive individuals, an earlier primary dysfunction of the NO system and a later production of oxidative stress cause age-related reduction in endothelium-dependent vasodilation. These alterations are similar but anticipated in hypertensive patients compared with normotensive subjects.

Topics: Acetylcholine; Adult; Age Factors; Aged; Ascorbic Acid; Drug Antagonism; Endothelium, Vascular; Enzyme Inhibitors; Female; Forearm; Humans; Hypertension; Male; Middle Aged; Nitric Oxide; Nitric Oxide Synthase; Nitroprusside; omega-N-Methylarginine; Oxidative Stress; Regional Blood Flow; Vasodilation; Vasodilator Agents

Left ventricular hypertrophy (LVH) is a cardiovascular risk factor. A possible role for endothelial dysfunction in this condition was investigated in a Dunkin-Hartley guinea pig aortic-banded pressure overload-induced model of LVH. Aortic banding produced significant elevation of fore- and hindlimb blood pressure (BP), heart-to-body weight ratios, plasma angiotensin II (ANG II), endothelin-1 (ET-1), tumor necrosis factor-alpha (TNF-alpha) levels, and coronary microvascular endothelial cell (CMEC) NAD(P)H-dependent superoxide (O) production, and a significant decrease in basal and stimulated CMEC cGMP levels. Treatment of aortic-banded animals with the angiotensin-converting enzyme inhibitor quinapril and the antioxidant vitamin C, either alone or in combination, did not affect BP but caused a significant inhibition of the increases in the heart-to-body weight ratio, ANG II, ET-1, and TNF-alpha levels, and O production and restored cGMP responses to levels comparable with sham-operated animals. These data suggest that quinapril and vitamin C are capable of inhibiting LVH development due to pressure overload via mechanisms that involve the inhibition of oxidative stress, an improvement in coronary endothelial function, and increased nitric oxide bioavailability.

Topics: Animals; Aortic Valve Stenosis; Ascorbic Acid; Blood Pressure; Coronary Vessels; Endothelium, Vascular; Guinea Pigs; Hypertension; Hypertrophy, Left Ventricular; Isoquinolines; Male; NAD; NADP; Quinapril; Superoxides; Tetrahydroisoquinolines

Ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) have antioxidant properties that could improve redox-sensitive vascular changes associated with hypertension. We determined whether vitamins C and E influence vascular function and structure in hypertension by modulating activity of NADPH oxidase and superoxide dismutase (SOD). Adult stroke-prone spontaneously hypertensive rats (SHRSP) were divided into 3 groups: control (C; n=6), vitamin C-treated (vit C, 1000 mg/day; n=7), and vitamin E-treated (vit E, 1000 IU/day; n=8). All rats were fed 4% NaCl. Blood pressure was measured weekly. After 6 weeks of treatment, the rats were killed, and mesenteric arteries were mounted as pressurized preparations. Vascular O(2)(-) generation and NADPH oxidase activity were measured by chemiluminescence. Vascular SOD activity and plasma total antioxidant status (TAS) were determined spectrophotometrically. Blood pressure increased from 212+/-7 to 265+/-6 mm Hg in controls. Treatment prevented progression of hypertension (vit C, 222+/-6 to 234+/-14 mm Hg; vit E, 220+/-9 to 227+/-10 mm Hg). Acetylcholine-induced vasodilation was improved (P<0.05), and media-to-lumen ratio was reduced (P<0.05) in the treated rats. O(2)(-) was lower in vitamin-treated groups compared with controls (vit C, 10+/-4 nmol. min(-1). g(-1) dry tissue weight; vit E, 9.6+/-3.5 nmol. min(-1). g(-1) dry tissue weight; C, 21+/-9 nmol. min(-1). g(-1) dry tissue weight; P<0.05). Both vitamin-treated groups showed significant improvement (P<0.01) in TAS. These effects were associated with decreased activation of vascular NADPH oxidase (vit C, 46+/-10; vit E, 50+/-9; C, 70+/-16 nmol. min(-1). g(-1) dry tissue weight, P<0.05) and increased activation of SOD (vit C, 12+/-2; vit E, 8+/-1; C, 4.6+/-1 U/mg; P<0.05). Our results demonstrate that vitamins C and E reduce oxidative stress, improve vascular function and structure, and prevent progression of hypertension in SHRSP. These effects may be mediated via modulation of enzyme systems that generate free radicals.

Topics: Acetylcholine; Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Blood Vessels; Dose-Response Relationship, Drug; Enzyme Activation; Hypertension; In Vitro Techniques; Mesenteric Arteries; NADPH Oxidases; Nitroprusside; Norepinephrine; Rats; Rats, Inbred SHR; Superoxide Dismutase; Superoxides; Vasoconstriction; Vasodilator Agents; Vitamin E

To investigate the effects of ascorbic acid deficiency on the pathogenesis of hypertension and/or its complications, we established a rat strain with both genetic hypertension and a defect of ascorbic acid biosynthesis. The od gene (L-gulono-gamma-lactone oxidase gene) of the ODS (Osteogenic Disorder Shionogi) rat, which is a rat mutant unable to synthesize ascorbic acid, was introduced into spontaneously hypertensive rats (SHR), and a novel congenic strain, SHR-od, was established. SHR-od showed scurvy when fed an ascorbic acid-free diet. Systolic blood pressure of male SHR-od began to increase at 9 weeks of age and reached 190-200 mmHg at 20 weeks of age. In 25-week-old SHR-od, ascorbic acid deficiency when fed an ascorbic acid-free diet for 6 weeks caused a remarkable reduction of blood pressure to lower than 110 mmHg. The wall to lumen ratio of the testicular artery in ascorbic acid-deficient SHR-od was lower than that of the control rats. When rats were fed a diet supplemented with ascorbic acid (300 mg/kg), ascorbic acid concentration in SHR-od was lower in the serum and liver than that in ODS rats. These results indicate that ascorbic acid could be closely related to the development of hypertension in SHR-od. We believe that SHR-od will be a useful model for experimental studies on hypertension and its complications, since all of them suffer from hypertension spontaneously and the level of ascorbic acid deficiency in these rats could be controlled at will both in concentration and duration.

Topics: Aging; Alkaline Phosphatase; Animals; Animals, Congenic; Arteries; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Pressure; Disease Models, Animal; Epinephrine; Heterozygote; Hypertension; L-Gulonolactone Oxidase; Liver; Male; Norepinephrine; Rats; Rats, Inbred SHR; Rats, Mutant Strains; Sugar Alcohol Dehydrogenases; Testis

Low-level lead exposure is a known cause of hypertension that has been associated with increased reactive oxygen species activity and endothelial-dependent vasorelaxation impairment. The effect of lead exposure on the vascular nitric oxide (NO)/cyclic guanocine monophosphate (cGMP) system was analyzed. Wistar rats were exposed to 5 ppm lead acetate in the drinking water during 30 d. Mean arterial BP increased significantly in the lead-treated rats. Relaxation to both acetylcholine and sodium nitroprusside (SNP) was reduced in lead-treated rats; however, the vascular wall of lead-administered rats showed an increased expression of endothelial NO synthase. The expression of both subunits (alpha(1) and beta(1)) of soluble guanylate cyclase (sGC) and the cGMP accumulated in the vascular wall were decreased in lead-treated rats. Cotreatment of lead with vitamin C (3 mmol/L) prevented the increase on mean arterial BP, improved the relaxation to both acetylcholine and sodium nitroprusside, and restored the normal expression of endothelial NO synthase and sGC proteins in the vascular wall. In conclusion, lead exposure altered both the endothelium-dependent and -independent relaxing response and induced a reduced expression of sGC in the vascular wall. These effects were abrogated with the antioxidant vitamin C, which suggests the involvement of reactive oxygen species in the regulation of the NO/cGMP relaxing system in the vascular wall of lead-treated rats.

Topics: Acetylcholine; Animals; Antioxidants; Ascorbic Acid; Blood Vessels; Endothelium, Vascular; Guanylate Cyclase; Hypertension; Lead; Male; Nitric Oxide Donors; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Nitroprusside; Rats; Rats, Wistar; Solubility; Vasodilation; Vasodilator Agents

Topics: Antioxidants; Ascorbic Acid; Clinical Trials as Topic; Humans; Hypertension

Topics: Administration, Oral; Antioxidants; Ascorbic Acid; Humans; Hypertension

Topics: Alprostadil; Antioxidants; Ascorbic Acid; Humans; Hypertension

Increased production of superoxide anion may contribute to impaired bioactivity of endothelium-derived nitric oxide in hypertension. Ascorbic acid is capable of scavenging superoxide anion; however, experimental studies have shown that high physiological concentrations (>1 mmol/L) of ascorbic acid are required to prevent superoxide-mediated vascular dysfunction. To seek kinetic evidence that superoxide anion contributes to endothelial vasomotor dysfunction in human hypertension, we examined the effects of 2.4 or 24 mg/min ascorbic acid intra-arterial infusions on forearm blood flow responses to methacholine or sodium nitroprusside in 30 patients with hypertension and 22 age-matched controls. Endothelium-dependent vasodilation to methacholine was significantly impaired in the hypertensive patients, with a response to the highest dose of methacholine (10 microg/min) of 12.3+/-6.7 compared with 16.1+/-5.8 mL. min(-1). dL tissue(-1) in the controls (P<0.001). The response to sodium nitroprusside was equivalent in the 2 groups. Ascorbic acid at 24 mg/min significantly improved the forearm blood flow response to methacholine in hypertensive patients with a peak response of 16.1+/-7.1 mL. min(-1). dL tissue(-1) (P=0.001). This dose produced a cephalic vein ascorbic acid concentration of 3.2+/-1. 4 mmol/L. In contrast, ascorbic acid at 2.4 mg/min had no effect on the methacholine response. Ascorbic acid at both doses had no effect on the vasodilator response to sodium nitroprusside in hypertensive patients or the methacholine response in the controls. These results agree with the predicted kinetics for superoxide anion-mediated impairment of endothelium-derived nitric oxide action. Thus, superoxide anion may contribute to impaired endothelium-dependent vasodilation in patients with hypertension.

Topics: Adult; Ascorbic Acid; Endothelium, Vascular; Female; Forearm; Free Radical Scavengers; Humans; Hypertension; Male; Middle Aged; Superoxides; Vasodilation

To study the relation between intake of the antioxidant flavonoid quercetin and subsequent incidence of cerebrovascular disease (CVA).. A cohort study carried out among 9208 Finnish men and women 15 y or more of age and initially free from cardiovascular disease. During a 28 y follow-up period in 1967-1994, a total of 824 cases with CVA were diagnosed.. Food consumption data were collected using a dietary history interview method covering the total habitual diet during the previous year.. Quercetin intake was not associated with CVA incidence. The relative risk of CVA adjusted for age, serum cholesterol, body mass index, smoking, hypertension, diabetes, geographical area, occupation and intake of beta-carotene, vitamin E, vitamin C, fibre, various fatty acids, and energy between the highest and lowest quartiles of quercetin intake was 0.99 (95% confidence interval (CI)=0.71-1.38) for men and 0.85 (CI=0.60-1.21) for women. In contrast, apples, the major source of quercetin in the study population, showed a significant inverse association both in men and women, mainly due to an association with thrombotic or embolic stroke. The relative risks of thrombotic stroke after further adjustment for quercetin intake were 0.59 (CI=0.35-0.99; P=0.45) and 0.61 (CI=0.33-1.12: P for trend=0.02) for men and women, respectively.. The results suggest that the intake of apples is related to a decreased risk of thrombotic stroke. This association apparently is not due to the presence of the antioxidant flavonoid quercetin.

Topics: Aging; Antioxidants; Ascorbic Acid; Body Mass Index; Cholesterol; Cohort Studies; Diet; Dietary Fiber; Energy Intake; Fatty Acids; Female; Fruit; Humans; Hypertension; Intracranial Thrombosis; Male; Quercetin; Risk Factors; Smoking; Stroke; Vitamin E

Several recent studies have shown that certain forms of genetic or acquired hypertension are associated with oxidative stress and that animals with those types of hypertension respond favorably to antioxidant therapy. We hypothesize that oxidative stress may cause hypertension via (among other mechanisms) enhanced oxidation and inactivation of nitric oxide (NO). To test this hypothesis, Sprague-Dawley rats were subjected to oxidative stress by glutathione (GSH) depletion by means of the GSH synthase inhibitor buthionine sulfoximine (BSO, 30 mmol/L in drinking water) for 2 weeks. The control group was given drug-free drinking water. In parallel experiments, subgroups of animals were provided vitamin E-fortified chow and vitamin C-supplemented drinking water. The BSO-treated group showed a 3-fold decrease in tissue GSH content, a marked elevation in blood pressure, and a significant reduction in the urinary excretion of the NO metabolite nitrate plus nitrite, which suggests depressed NO availability. These characteristics were associated with a significant accumulation in various tissues of nitrotyrosine, which is the footprint of NO inactivation by reactive oxygen species. Administration of vitamin E plus vitamin C ameliorated hypertension, improved urinary nitrate-plus-nitrite excretion, and mitigated nitrotyrosine accumulation (despite GSH depletion) in the BSO-treated animals but had no effect in the control group. In conclusion, GSH depletion resulted in perturbation of the NO system and severe hypertension in normal animals. The effects of BSO were mitigated by concomitant antioxidant therapy despite GSH depletion, which supports the notion that oxidative stress was involved in the pathogenesis of hypertension in this model.

Topics: Animals; Antioxidants; Ascorbic Acid; Buthionine Sulfoximine; Glutathione; Hypertension; Male; Nitric Oxide; Oxidative Stress; Rats; Rats, Sprague-Dawley; Vitamin E

Noradrenergic vascular hyper-responsiveness is a hallmark of essential hypertension. To evaluate whether nitric oxide plays a role in the enhanced vascular response to norepinephrine in hypertension, we examined 32 hypertensives and 28 normotensives who were distributed in 3 experimental series.. In the first series, we measured the forearm blood flow (FBF) response to a norepinephrine infusion under control conditions and during the infusion of L-N-monomethylarginine (L-NMMA). Norepinephrine evoked dose-dependent vasoconstriction that was greater in hypertensives than in normotensives (maximum FBF, -61+/-1 versus -51+/-1%; P<0.01). During L-NMMA infusion, norepinephrine vasoconstriction was not modified in hypertensives; however, it was potentiated in normotensives (maximum FBF, -64+/-2%; P<0.01). In the second series, we tested whether norepinephrine vasoconstriction could be affected by an antioxidant such as ascorbic acid. Norepinephrine vasoconstriction was blunted by ascorbic acid administration only in hypertensives (maximum FBF, -49+/-3 versus -63+/-2%; P<0.01); the vasoconstriction became similar to that observed in normotensives. During ascorbic acid plus L-NMMA administration, the vascular response to norepinephrine increased to a similar extent in both study groups. To rule out the possibility that the effect of ascorbic acid on norepinephrine vasoconstriction could depend on adrenergic receptor-induced nitric oxide release, in the last series we inhibited endogenous nitric oxide and replaced it with an exogenous nitric oxide donor (sodium nitroprusside). Even in these conditions, ascorbic acid attenuated norepinephrine vasoconstriction only in hypertensives (maximum FBF, -50+/-2 versus -62+/-1%; P<0.01).. Our data demonstrate that noradrenergic vascular hyper-responsiveness in hypertension is dependent on an impairment of nitric oxide activity that is realized through norepinephrine-induced oxygen free radical production.

Topics: Adult; Ascorbic Acid; Blood Pressure; Female; Forearm; Humans; Hypertension; Infusions, Intravenous; Male; Nitric Oxide; Norepinephrine; omega-N-Methylarginine; Reference Values; Regional Blood Flow; Vasoconstriction

The influence of anti-atherosclerotic diet with including some biologically active additives, with contain vitamins C, E, beta-carotene, Zn, Cr, Se was studied in 80 patients with ischemic heart disease, hypertension disease. The usage of biologically active additives during 4 weeks has promoted positive changes of clinical symptoms of diseases against a background of lowering of serum cholesterol, triglycerides and increasing of IgA, IgG, vitamins A, E, C.

Topics: Adult; Ascorbic Acid; Cholesterol; Chromium; Complement C3; Diet, Reducing; Female; Humans; Hypertension; Immunoglobulins; Male; Middle Aged; Minerals; Myocardial Ischemia; Obesity; Selenium; Triglycerides; Vitamin E; Vitamins; Zinc

In 9 patients with essential hypertension, we tested whether a high-dose (12 mg. min(-1)) vitamin C infusion into the brachial artery, by improving endothelium-dependent vasodilatation, would also attenuate the insulin resistance of deep forearm tissues. We measured the effect of vitamin C on acetylcholine (Ach)-induced vasodilatation and on forearm glucose uptake during systemic hyperinsulinemia; in all studies, the contralateral forearm served as the control. Intrabrachial Ach infusion produced a stable increase in forearm blood flow, from 2.6+/-0.3 to 10.6+/-2.1 mL. min(-1). dL(-1); when vitamin C was added, a further rise in forearm blood flow (to 13.4 mL. min(-1). dL(-1); P<0.03 vs Ach alone) was observed. In response to insulin, blood flow in both the infused and control forearms did not significantly change from baseline values (+10+/-16% and +2+/-11%, respectively). In contrast, when vitamin C was added, blood flow in the infused forearm increased significantly (to 3.7+/-0.7 mL. min(-1). dL(-1); P<0.02 vs 2.8+/-0.6 mL. min(-1). dL(-1) in the control forearm). Insulin stimulated whole-body glucose disposal to 20+/-2 micromol. min(-1). kg(-1), compatible with the presence of marked insulin resistance. Forearm glucose uptake was similarly stimulated after 80 minutes of insulin infusion (to 2.11+/-0.42 and 2.06+/-0.43 micromol. min(-1). dL(-1), infused and control, respectively). When intrabrachial vitamin C was added, no difference in glucose uptake was observed between the 2 forearms (infused, 2.37+/-0.44 micromol. min(-1). dL(-1)and control, 2.36+/-0. 53 micromol. min(-1). dL(-1)). Forearm O(2) uptake at baseline was also similar in the 2 forearms (infused, 9.7+/-0.7 micromol. min(-1). dL(-1) and control, 9.6+/-1.1 micromol. min(-1). dL(-1)) and was not changed by either insulin or vitamin C. We conclude that in the deep forearm tissues of patients with essential hypertension and insulin resistance, an acute improvement in endothelial function, obtained with pharmacological doses of vitamin C, restores insulin-mediated vasodilatation but does not improve insulin-mediated glucose uptake. Thus, the endothelial dysfunction of essential hypertension is unlikely to be responsible for their metabolic insulin resistance.

Topics: Ascorbic Acid; Blood Flow Velocity; Blood Glucose; Forearm; Humans; Hypertension; Infusions, Intra-Arterial; Insulin; Insulin Resistance; Male; Middle Aged; Regional Blood Flow; Vasodilation

Many changes in endothelial function have been described in hypertension. Endothelium-dependant dilatation due to the stimulation of specific receptors or related to changes in flow, are reduced both in experimental models and in clinical observations of hypertensive patients. Many mechanisms of this endothelial dysfunction have been proposed. Reduction of the activity of the enzyme synthesising nitric oxide has been found in some animal modes of hypertension (salt-related) and in hypertensive subjects whereas in other experimental models, this enzyme's activity is increased. Other mechanisms, therefore, play a role, such as increased synthesis of constricting prostanoids and increased synthesis of oxygen radicals. The inhibition of cyclooxygenase or intra-arterial administration of Vitamin C in hypertensive patients may restore endothelium-dependant vasodilatation. In view of the many endothelium-dependant mechanisms described in the pathogenesis of hypertension, the authors underline the fact that in most studies each mechanism has been studied individually. However, understanding the interactions of the different endothelial dependant mechanisms is the key to reconciling the many physiopathological disturbances observed in hypertension, differentiating direct from indirect changes induced by the complex network of interactions one with another. This will also result in a more accurate appreciation of the similarities and differences of effects of antihypertensive drug therapy targeted on endothelial function.

Topics: Animals; Ascorbic Acid; Disease Models, Animal; Endothelium; Free Radicals; Humans; Hypertension; Nitric Oxide Synthase; Vasodilation

Low-density lipoprotein oxidation and antioxidant vitamins E and C were investigated in dipper (nocturnal blood pressure fall > 10%) and nondipper (nocturnal blood pressure fall < 10%) hypertensives. We studied 40 dippers and 28 nondippers balanced for gender, age, and body mass index. Blood samples were drawn for lipid profile determination, assessment of thiobarbituric acid-reactive substances, and fluorescent products of lipid peroxidation in native low-density lipoprotein, evaluation of susceptibility to low-density lipoprotein oxidation in vitro (lag phase and propagation rate), and determination of low-density lipoprotein vitamin E and plasma vitamins E and C contents. Compared with dippers, nondippers had significantly higher thiobarbituric acid-reactive substances and fluorescent products of lipid peroxidation (0.63 +/- 0.1 v 0.77 +/- 0.08 nmol malondialdehyde/mg low-density lipoprotein protein, and 14.5 +/- 6 v 17.9 +/- 4 units of relative fluorescence/mg low-density lipoprotein protein, respectively, both P < .05), shorter lag phase (56 +/- 13 v 49 +/- 9 min, P < .05), and lower plasma vitamin C content (42 +/- 9 v 35 +/- 10 micromol/L, P < .05). When gender was taken into account, differences were not significant between dipper and nondipper men, whereas, compared with dipper women, nondipper women showed significantly higher thiobarbituric acid-reactive substances and fluorescent products of lipid peroxidation (0.56 +/- 0.1 v 0.77 +/- 0.07 nmol malondialdehyde/mg low-density lipoprotein protein, and 12.5 +/- 4 v 17.5 +/- 4.6 units of relative fluorescence/mg low-density lipoprotein protein, respectively, both P < .05), shorter lag phase (62.5 +/- 11 v 49 +/- 9.5 min, P < .05), and lower plasma vitamin C content (44.9 +/- 10 v 34.7 +/- 10.8 micromol/L, P < .05). Given the role of low-density lipoprotein oxidation in the pathogenesis of atherosclerosis and that of vitamin C in protecting against it, our data suggest that nondippers, especially among women, show higher atherogenic risk than dippers.

Topics: Adult; Ascorbic Acid; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cholesterol; Cholesterol, LDL; Circadian Rhythm; Female; Humans; Hypertension; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Thiobarbituric Acid Reactive Substances; Triglycerides; Vitamin E

In essential hypertension, endothelium-dependent vasodilation is impaired because of reduced nitric oxide (NO) availability, which is mainly caused by oxidative stress. The present study was designed to identify the mechanism(s) responsible for NO-independent vasodilation to bradykinin in patients with essential hypertension.. In 16 healthy subjects (49.5+/-5.8 years; 118.6+/-3.5/78.9+/-2.9 mm Hg) and 16 patients with essential hypertension (47.9+/-4.8 years; 154.6+/-4.5/102.9+/-3.2 mm Hg), we measured modifications in forearm blood flow (strain-gauge plethysmography) during intrabrachial infusion of bradykinin (5, 15, or 50 ng/100 mL of forearm tissue per minute) in the presence of saline, N(omega)-monomethyl-L-arginine (L-NMMA; used to inhibit NO synthase; 100 microg/100 mL of forearm tissue per minute), and ouabain (to block Na(+)K(+)/ATPase and prevent hyperpolarization; 0.7 microg/100 mL of forearm tissue per minute). In healthy subjects, vasodilatation to bradykinin was significantly blunted by L-NMMA and unaffected by ouabain. In hypertensive patients, vasodilatation to bradykinin was not modified by L-NMMA, but it was significantly reduced by ouabain. In an adjunctive group of 8 hypertensive patients (49.9+/-3.8 years; 155.9+/-5.5/103.7+/-3.9 mm Hg), the response to bradykinin was repeated during the administration of intrabrachial vitamin C (a scavenger for oxygen free radicals; 8 mg/100 mL of forearm tissue per minute). In these patients, L-NMMA-induced inhibition of vasodilation to bradykinin was restored, and ouabain was no longer effective. In a final group of 6 normotensive controls (45.9+/-4.1 years; 115.1+/-2.9/79.3+/-2.1 mm Hg), vasodilation to bradykinin residual to L-NMMA blockade was further inhibited by simultaneous ouabain infusion.. Vasodilation to bradykinin is impaired in essential hypertensive patients because of an NO-system alteration caused by oxidative stress, and it is mediated by an alternative pathway, possibly involving endothelium-dependent hyperpolarization.

Topics: Adaptation, Physiological; Adult; Antioxidants; Ascorbic Acid; Biological Availability; Bradykinin; Drug Combinations; Enzyme Inhibitors; Female; Humans; Hypertension; Male; Middle Aged; Nitric Oxide; Nitroprusside; omega-N-Methylarginine; Ouabain; Reference Values; Vasodilation; Vasodilator Agents

Topics: Ascorbic Acid; Coronary Circulation; Endothelium, Vascular; Humans; Hypercholesterolemia; Hypertension; Infusions, Intravenous; Vascular Resistance

There is evidence that formation of free radicals increases in patients with hypertension or hypercholesterolaemia, which may contribute to endothelial dysfunction of epicardial coronary arteries due to inactivation of the vasodilator NO. The present study was designed to test whether the abnormal constriction of epicardial coronary arteries due to sympathetic stimulation by the cold pressor test in patients with essential hypertension or hypercholesterolaemia could be reversed by administration of the antioxidant vitamin C.. In 28 patients without relevant coronary artery stenosis the cold pressor test was performed before and after a 3 g infusion of vitamin C. In five normal controls the cold pressor test led to a similar increase in luminal area before and after vitamin C (3.7+/-1.3% and 1.9+/-0.8%, ns vs before vitamin C). In nine hypercholesterolaemic patients the cold pressor test led to a -14.1+/-2.8% reduction in cross-sectional area before vitamin C. This constriction was significantly improved after vitamin C to -7.6%+/-2.0, P=0.027 vs before vitamin C. In nine hypertensive patients, the cold pressor test led to a -17.1+/-3.2% decrease in cross-sectional area before vitamin C, which was improved to -7.1+/-3.1 after vitamin C, P=0.004 vs before vitamin C. This increase in luminal area was significant in each group in comparison with normal controls (each P<0.05). Administration of saline (placebo group, five patients) had no significant effect on cold pressor test-induced constriction (-6.9+/-3.9% before and -6. 8+/-3.7% after saline).. The antioxidant vitamin C reverses cold pressor test-induced vasoconstriction of epicardial coronary arteries in patients with hypertension or hypercholesterolaemia. Our data suggest that enhanced oxidative stress contributes to impaired endothelial function in this patient population.

Topics: Aged; Ascorbic Acid; Cold Temperature; Coronary Vessels; Endothelium, Vascular; Female; Humans; Hypercholesterolemia; Hypertension; Infusions, Intravenous; Male; Middle Aged; Oxidative Stress; Vascular Resistance

Low-density lipoprotein oxidation and antioxidant vitamins E and C were investigated in white-coat hypertension in comparison with sustained hypertension and normotension. We selected 21 sustained hypertensive subjects, 21 white-coat hypertensive subjects, and 21 normotensive subjects matched for gender, age, and body mass index. White-coat hypertension was defined as clinical hypertension and daytime ambulatory blood pressure <139/90 (subjects were also reclassified using 134/90 and 135/85 mm Hg as cutoff points for daytime blood pressure). Blood samples were drawn for lipid profile determination, assessment of fluorescent products of lipid peroxidation in native LDL, evaluation of susceptibility to LDL oxidation in vitro (lag phase and propagation rate), and determination of LDL vitamin E and plasma vitamins E and C contents. Compared with sustained hypertensive subjects, white-coat hypertensives had significantly lower fluorescent products of lipid peroxidation (15.4+/-3.4 versus 10.2+/-3 units of relative fluorescence/mg LDL protein, P<.05), longer lag phase (54+/-10 versus 88+/-10 minutes, P<.05), lower propagation rate (8.2+/-2.5 versus 5.95+/-2.1 nmol diene/min per mg LDL cholesterol, P<.05), higher LDL vitamin E content (8.3+/-1.1 versus 10.1+/-1.8 nmol/mg LDL cholesterol, P<.05), and plasma vitamin C content (40+/-13 versus 57+9 micromol/L, P<. 05). No significant difference was observed between white-coat hypertensive and normotensive subjects. The results did not change after reclassification of subjects. Our data show that white-coat hypertensive subjects do not show an enhanced propensity to LDL oxidation or reduction in antioxidant vitamins. Given the role of LDL oxidation in the development of atherosclerosis and that of vitamin E and C in protecting against it, these findings suggest that white-coat hypertension per se carries a low atherogenic risk.

Topics: Adult; Ascorbic Acid; Blood Pressure; Blood Pressure Determination; Blood Pressure Monitoring, Ambulatory; Female; Humans; Hypertension; Lipoproteins, LDL; Male; Middle Aged; Office Visits; Reference Values; Vitamin E

In diabetic nephropathy and hypertension, a major cause of mortality is from cardiovascular disease. Since low levels of antioxidants such as vitamin C have been associated with such complications, we have examined the uptake mechanisms for ascorbic acid (AA) and dehydroascorbic acid (DHA) in lymphoblasts from normal control subjects (CON), normoalbuminuric insulin-dependent diabetic (IDDM) patients (DCON), patients with IDDM and nephropathy (DN) and hypertensive patients (HT) using mass assays of uptake and measuring AA using high-performance liquid chromatography. Precautions were taken to prevent oxidation of AA and to take into account the instability of DHA in buffers. DHA uptake was the major mechanism in all four groups of subjects, and the Vmax (maximal uptake rate) was significantly lower in the DN cells (24.7 +/- 1.0 nmol [95% confidence intervals CI 22.5, 26.3] 10(6) cells(-1) h(-1)) compared to CON and DCON cells (33.9 +/- 2.1 [95% CI 29.4, 38.4] and 37.0 +/- 2.2 [95% CI 32.2, 41.8] nmol 10(6) cells(-1) h(-1), respectively, p < 0.001 for both). DHA Vmax was also lower in the HT group (23.2 +/- 1.1 [95% CI 20.7, 25.7] nmol 10(6) cells(-1) h(-1)) compared to the CON group (p < 0.001). There were no significant differences in the Km or passive membrane permeability for DHA or the AA uptake. DHA uptake showed a negative correlation to systolic blood pressure (r(s) = -0.49, p < 0.001). These findings suggest that impaired DHA uptake may be one component of the phenotype expressed by DN cells that may persist in culture. Impaired DHA uptake in vivo, especially in the presence of hyperglycaemia, leads to impaired regeneration of AA and depletion of anti-oxidant defences, exposing such individuals to increased risk of cardiovascular disease.

Topics: Adult; Aged; Albuminuria; Ascorbic Acid; Biological Transport; Cells, Cultured; Dehydroascorbic Acid; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Humans; Hypertension; Kinetics; Male; Middle Aged; Models, Biological; Reference Values

To characterize relationships among blood pressure, pulse rate, vitamin C status and other protective and risk factors for older British people, from a national survey.. A cross-sectional analysis of survey data.. A population study, representative of mainland Britain.. Among 914 people of both sexes living in the community, 373 were taking blood-pressure-lowering drugs and were therefore excluded from the analyses.. Completion of an interview on health, lifestyle and dietary habits, recording of a 4-day dietary record, anthropometry and taking of a blood sample to determine haematological and biochemical status.. Systolic and diastolic blood pressures, pulse rate, indices of micronutrient status including plasma ascorbate concentration, nutrient intake and haematology.. Plasma ascorbate concentration was inversely correlated to systolic and diastolic blood pressures and pulse rate. Other covariates of blood pressure included age, sex, domicile, plasma retinol, fibrinogen and gamma-tocopherol concentrations, erythrocyte count, prothrombin time and urine sodium: creatinine ratio. Covariates of pulse rate included sex, domicile, plasma fibrinogen and platelet count. Blood pressure was also correlated to intake of vitamin C.. Plasma ascorbate concentration and intake of vitamin C are covariates of blood pressure in older people living in Britain. New intervention studies are now needed, to test for possible causalities.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Blood Pressure; Cross-Sectional Studies; Data Collection; Diastole; Diet; Female; Heart Rate; Humans; Hypertension; Male; Systole; United Kingdom

In polymorphonuclear granulocytes of men which used nifedipine in daily doses 30 mg during the period of 7 days was found: after 3 days as well after 7 days the lower concentration of copper and the higher concentration of zinc. The vitamin C concentration did not change substantially.

Topics: Adult; Ascorbic Acid; Calcium Channel Blockers; Copper; Humans; Hypertension; Male; Middle Aged; Neutrophils; Nifedipine; Zinc

Amyloidosis results from protein infiltration of the extracellular space of organs and tissues. Several amyloidosis proteins have been identified. Protein AL, (deriving from immunoglobulin light chain), protein AA and prealbumin are the most involved in this disease. When AL amyloidosis involves the heart, the illness is often terminal. Most clinical symptoms are heart failure and arrhythmia or block conduction. This case was characterised by the unusual combination of hypertension and amyloidosis. The diagnosis suggested by the echocardiographic but was confirmed by the damaged organ's biopsy. The present case concerns a young woman, who has hypertension and a pulmonary oedema. The echocardiographic scan showed a septal hypertrophy with a shining and granite-like aspect which is compatible with heart amyloidosis. Systolic and diastolic disorder with mitral and aortic regurgitation were also revealed. The kidney and rectum biopsies confirmed amyloidosis AL of the Kappa dysglobulinemia type, without extraosseous plasmocytoma. The heart and kidney failure symptoms disappeared after treatment with diuretics and ACE inhibitors.

Topics: Adult; Amyloidosis; Angiotensin-Converting Enzyme Inhibitors; Ascorbic Acid; Biopsy; Cardiomegaly; Colchicine; Diuretics; Echocardiography; Female; Heart Failure; Heart Valve Diseases; Humans; Hypertension; Immunoglobulin kappa-Chains; Nephritis; Paraproteinemias; Pulmonary Edema; Radiography; Rectum

There are increasing evidences that fish oil-enriched diets attenuate the progression of several types of human and experimental renal, intestinal and cardiovascular disorders including hypertension. Docosahexaenoic acid (DHA) may be one of the active biological component. We previously reported that dietary DHA suppressed the progression of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). The purpose of this study was to clarify the in vitro effect of DHA on vascular smooth muscle cell functions such as cell growth, hypertrophy, NO release, and intracellular Ca+2 dynamics which involves in the regulatory mechanisms of vascular tone. Addition of DHA to the culture medium of aortic smooth muscle cells isolated from SHRSP and normotensive Wistar Kyoto rats (WKY) had no significant effects on the cell growth, and cell hypertrophy induced by angiotensin II as measured by flow cytometer. DHA did not have a significant effect on interleukin-1 beta (10 ng/ml)-induced nitric oxide release from smooth muscle cells of SHRSP. However, the treatment of smooth muscle cells with DHA (30 microM) for 2 days significantly suppressed the increase in the intracellular Ca2+ concentration induced by 5-hydroxytryptamine, angiotensin II, depolarizing concentration of KCl, but not by thapsigargin. This suppression seems to be due to the suppression of Ca2+ influx, as determined by Mn2+ influx experiment. These results suggest that DHA specifically suppresses receptor-mediated Ca2+ influx in smooth muscle cells. This may be one of the mechanisms by which dietary DHA prevents the development of hypertension in SHRSP.

Topics: Animals; Ascorbic Acid; Calcium; Cell Division; Cells, Cultured; Docosahexaenoic Acids; Hypertension; Male; Muscle, Smooth, Vascular; Nitric Oxide; Phosphatidylinositols; Rats; Rats, Inbred SHR; Rats, Inbred WKY

Hypertension is associated with an increased risk of atherosclerosis. Free radical oxidative damage has been implicated in the atherogenic process. We measured levels of the antioxidants uric acid, thiols, vitamins C, A and E as well as the total antioxidant capacity in 21 normotensive controls, 22 patients whose hypertension was controlled on drugs and 30 patients with uncontrolled hypertension. Mean BPs in the groups were 125/76, 132/80 and 181/98 mmHg, respectively. When compared with controls, both hypertensive groups had significantly lower serum ascorbic acid (54 +/- 5 vs. 37 +/- 6 vs. 38 +/- 5 mumol/l, P < 0.05) and albumin-corrected thiol levels (9.91 +/- 0.18 vs. 8.69 +/- 0.20 vs. 8.92 +/- 0.19 mumol/g, P < 0.05). The levels of the other antioxidants did not differ significantly between the groups. Levels of von Willebrand factor, a marker of endothelial damage, were correlated with SBP but not with antioxidant status. We conclude that hypertensive subjects have lower levels of the antioxidants vitamin C and thiols and this may reflect greater oxidative consumption. The implications for atherogenesis and endothelial function and integrity in hypertension are discussed.

Topics: Adult; Aged; Analysis of Variance; Antihypertensive Agents; Antioxidants; Arteriosclerosis; Ascorbic Acid; Biomarkers; Endothelium, Vascular; Female; Free Radical Scavengers; Humans; Hypertension; Male; Middle Aged; Uric Acid; Vitamin A; Vitamin E; von Willebrand Factor

Plasma lipid and apolipoprotein (apo) A-I and B concentrations and habitual dietary intakes were determined in 306 free-living elderly individuals (119 men and 187 women, age range 60-100 y). Plasma lipid and apo A-I concentrations were significantly higher in women than in men. In older men, plasma triglyceride, total cholesterol, and apo B concentrations were significantly lower than in younger men, whereas a significant trend towards lower LDL-cholesterol concentrations was observed in older women. Energy intake and percent macronutrient intake were not influenced by age. Higher carbohydrate intake was associated with lower HDL cholesterol and apo A-I concentrations, whereas higher total fat intake was associated with higher apo A-I concentrations. Higher vitamin A intake was associated with higher plasma concentrations of HDL cholesterol and apo A-I. Our data indicate that both dietary and plasma concentrations of vitamin A, body mass index, age, and sex are important determinants of plasma lipid concentrations in the elderly.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Apolipoproteins; Ascorbic Acid; Body Mass Index; Body Weight; Coronary Disease; Diabetes Mellitus; Diet; Diet Surveys; Female; Humans; Hypertension; Lipids; Lipoproteins; Male; Middle Aged; Vitamin A

Topics: Animals; Ascorbic Acid; Blood Pressure; Clinical Trials as Topic; Humans; Hypertension; Scurvy

The biochemical mechanisms by which hypertension accelerates atherosclerosis and increases the risk of aortic aneurysm rupture are poorly understood. This study evaluates the effects of hypertension on aortic trace element concentrations and antioxidant status in tissue removed from 26 normotensive (NT) and 20 hypertensive (HT) patients. Twenty-seven of 46 patients (59%) had aneurysmal (AA), and 19 of 46 (41%) had occlusive disease (OD). Aortic iron concentrations were markedly higher in both OD and AA tissue compared with controls. A similar trend was observed with copper concentrations, with the highest elevations observed in HT AA tissues. No significant differences were observed in zinc concentrations, except that HT AA aorta had significantly lower zinc levels than either OD or control tissue. Aortic ascorbic acid concentrations in diseased aorta were lower than those of controls, but independent of blood pressure. Copper-zinc-superoxide dismutase activity was similarly reduced, with the lowest activity observed in diseased aorta from HT patients. Only HT AA aorta had significantly higher manganese-superoxide dismutase activity than controls. The aortas of patients with AA had significantly lower amounts of elastin and greater elastase activity than either controls or those with OD. However, the differences were independent of blood pressure. Hypertensive patients with OD and AA had 31% more and 27% less aortic collagen, respectively, than their NT counterparts (P less than 0.05). These data suggest that the reduction in aortic collagen and elastin in HT patients with AA compared with their NT counterparts may explain the larger size of aneurysms and predispose to their eventual rupture. Furthermore, the diminished antioxidant status associated with HT predisposes to lipid peroxidation, which contributes to the acceleration of these processes. Our studies were conducted in patients with established aortic aneurysmal and occlusive disease. Whether these observations are pertinent to the pathogenesis of AA and OD remains unclear and merits further study.

Topics: Antioxidants; Aorta; Aortic Aneurysm; Arteriosclerosis; Ascorbic Acid; Blood Pressure; Collagen; Copper; Elastin; Humans; Hypertension; Iron; Lipid Peroxidation; Male; Superoxide Dismutase; Trace Elements; Zinc

Topics: Ascorbic Acid; Humans; Hypertension

Topics: Aging; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Pressure; Cerebrovascular Disorders; Diabetes Complications; Diet, Vegetarian; Humans; Hypertension; Prevalence; United States

Data from the first National Health and Nutrition Examination Survey collected between 1971 and 1972 were used to determine what factors are associated with the prevalence of age-related macular degeneration. The study was limited to those who were at least 45 years old at the time of the ophthalmology examination. Stratified analysis, adjusting for age, showed that education, systolic blood pressure, past history of hypertension, cerebrovascular disease, and refractive error were all associated with macular degeneration. With the exception of education, these factors remained statistically significant when simultaneously entered into a logistic regression model. The frequency of consumption of fruits and vegetables rich in vitamins A and C suggested a negative association with the prevalence of macular degeneration after stratified adjustment for age. In a logistic regression analysis, adjusting for demographic and medical factors, the inverse association of vitamin C with age-related macular degeneration was no longer present. The frequency of consumption of fruits and vegetables rich in vitamin A remained negatively correlated with age-related macular degeneration even after adjustment for demographic and medical factors.

Topics: Age Factors; Aged; Ascorbic Acid; Female; Fruit; Health Surveys; Humans; Hypertension; Macular Degeneration; Male; Middle Aged; United States; Vegetables; Vitamin A

Spontaneously hypertensive rats (SH rats) were administered drinking water containing 0, 200 or 1000 ppm ascorbic acid with or without 0.5% NaCl and the usual laboratory stock diet for 130 days. The rats given ascorbic acid with or without 0.5% NaCl had a lower mean systolic blood pressure level than that of the respective control group. The difference in the mean blood pressure level from that of the control group was 18-19 mmHg for 200 ppm ascorbic acid group and 30-40 mmHg for 1000 ppm ascorbic acid group. The SH rats were shown to have some defects of ascorbic acid metabolism by lower tissue ascorbic acid levels in the liver, lung and adrenals, and by lower response of ascorbic acid synthesis to a xenobiotic than the Wistar Kyoto rats, which served as the normotensive control rats for SH rats. The abnormalities of ascorbic acid metabolism in the SH rats may be associated with, in part, their high blood pressure, because exogenous ascorbic acid prevented the blood pressure elevation of SH rats, but some other mechanism may also be involved in the effect of ascorbic acid on blood pressure.

Topics: Animals; Ascorbic Acid; Blood Pressure; Hypertension; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Tissue Distribution

Correlation analyses between serum ascorbic acid and several risk factors of cerebro- and cardio-vascular diseases were performed on apparently healthy adults (194 persons) aged 30-39 in order to estimate possible functions of ascorbic acid in the prevention of the disease. Serum ascorbic acid had an inverse and the strongest association with systolic blood pressure among the risk factors including blood pressure, total cholesterol, triglyceride, gamma-GTP and obesity. The association was independent of the other variables tested. When the subjects were divided into three different serum ascorbic acid level groups, the prevalence of hypertension (140/90 mmHg and above) was decreased with an increase in the ascorbic acid level. The close relationship of serum ascorbic acid and blood pressure observed in the study suggests that ascorbic acid may have a preventive function against hypertension, or a low ascorbic acid status in hypertensives may promote the further development of arteriosclerosis by the lack of favorable effect of ascorbic acid on lipid metabolism and others.

Topics: Adult; Ascorbic Acid; Blood Pressure; Cholesterol; Cholesterol, HDL; gamma-Glutamyltransferase; Humans; Hypertension; Male

A data base of the National Center for Health Statistics, Health and Nutrition Examination Survey I (HANES I), was used to perform a computer-assisted, comprehensive analysis of the relation of 17 nutrients to the blood pressure profile of adult Americans. Subjects were 10,372 individuals, 18 to 74 years of age, who denied a history of hypertension and intentional modification of their diet. Significant decreases in the consumption of calcium, potassium, vitamin A, and vitamin C were identified as the nutritional factors that distinguished hypertensive from normotensive subjects. Lower calcium intake was the most consistent factor in hypertensive individuals. Across the population, higher intakes of calcium, potassium, and sodium were associated with lower mean systolic blood pressure and lower absolute risk of hypertension. Increments of dietary calcium were also negatively correlated with body mass. Even though these correlations cannot be accepted as proof of causation, they have implications for future studies of the association of nutritional factors and dietary patterns with hypertension in America.

Topics: Adolescent; Adult; Age Factors; Aged; Ascorbic Acid; Blood Pressure; Calcium; Energy Intake; Female; Humans; Hypertension; Male; Middle Aged; National Center for Health Statistics, U.S.; Nutrition Surveys; Nutritional Physiological Phenomena; Obesity; Potassium; Racial Groups; Sex Factors; Sodium; United States; Vitamin A

Topics: Adult; Ascorbic Acid; Blood Pressure; Female; Humans; Hypertension; Lipids; Sodium

Hypertension-prone, male, spontaneously hypertensive rats (SHR; n = 60) and normotensive, male, Sprague-Dawley rats (S-D; n = 60) were exposed to the relatively innocuous stimulus of heat and ether when they were 40 days of age, just before the usual onset of high blood pressure in SHR. The animals were decapitated 0, 2, 5, 15, and 60 min postexposure to heat and ether. Blood levels of corticosterone, aldosterone, PRL, GH were measured concomitant with pituitary content of GH and PRL and adrenal content of ascorbic acid and cholesterol. The foregoing constituents were used as an index of pituitary-adrenal responsiveness. Changes in circulating corticosterone, PRL, GH, and especially aldosterone indicated that before the onset of their high blood pressure, SHR are much more responsive to noxious stimuli than normotensive S-D. The pattern of change in the pituitary content of GH and PRL, adrenal ascorbate, and cholesterol were also indicative of SHR hypersensitivity. These findings suggest that adrenal steroidogenesis and the stress response pattern in SHR vs. normotensive rats may be unique.

Topics: Adrenal Glands; Aldosterone; Animals; Ascorbic Acid; Blood Pressure; Cholesterol; Corticosterone; Ether; Ethyl Ethers; Growth Hormone; Hot Temperature; Hypertension; Male; Prolactin; Rats; Rats, Inbred Strains; Time Factors

Topics: Appetite Depressants; Ascorbic Acid; Humans; Hypertension; Nonprescription Drugs; Psychoses, Substance-Induced; Sympathetic Nervous System

Young adult male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats were killed under strictly quiescent conditions when they became 24, 32, 44, 60, 90 and 120 days of age. Systolic blood pressure was measured just prior to autopsy. Adrenal glands were assayed for ascorbic acid and total cholesterol content, and examined histologically. At 60 days of age, the blood pressure of the SHR became abnormally elevated, reaching severely elevated levels by 120 days of age. The adrenal glands of SHR were consistently smaller than those of WKy but their zonae glomerulosae stained intensively positive for lipid. Adrenocortical ascorbate and cholesterol content remained consistently and significantly lower in SHR vs WKy as did circulating corticosterone levels. Plasma aldosterone levels rose concomitantly with rising blood pressure in SHR and became progressively lower with age in normotensive WKy. These findings suggest that corticosteroidogenesis is different in SHR vs normotensive WKy rats.

Topics: Adrenal Glands; Aldosterone; Animals; Ascorbic Acid; Cholesterol; Corticosterone; Hypertension; Male; Organ Size; Rats; Rats, Inbred Strains

Kainic acid (KA), an analogue of L-glutamate, was microinjected in 0.1 microliter of saline into the nucleus tractus solitarii (NTS) of adult rats. In rats anesthetized with halothane or alpha-chloralose, KA injected unilaterally elicited hypotension, bradycardia, and apnea. The threshold dose was 0.1-0.2 ng (10(-13) mol). Doses greater than 0.2 ng blocked responses to subsequent injections for at least 30 minutes. Doses of KA greater than 15 ng reduced the reflex bradycardia elicited by raising the arterial pressure with phenylephrine and produced arterial hypertension in rats anesthetized with alpha-chloralose or in other rats within 15 minutes of terminating halothane anesthesia. Bilateral injection of KA in doses greater than 15 ng completely blocked baroreflexes and resulted in a dose-dependent elevation of arterial pressure (167 +/- 9.4; P less than 0.001) both in alpha-chloralose-anesthetized rats and in awake rats after the termination of halothane anesthesia. The hypertension rapidly led to pulmonary edema and death. Procaine microinjected also elicited fulminating hypertension; vehicle did not. Doses of KA producing hypertension caused no histological or biochemical evidence of neuronal death. The cardiovascular responses to KA were restricted to sites in the intermediate one-third of NTS and could not be elicited by injection into adjacent sites in brainstem. The results indicate that, in low doses, KA injected into NTS stimulates neurons which mediate the baroreflex, whereas, in higher doses, it produces baroreflex blockade and neurogenic hypertension. The results suggest that fulminating hypertension can be produced by nondestructive perturbations of neurochemical transmission in brain. Since the cardiovascular responses of KA are similar to those produced by microinjection into NTS of the amino acid neurotransmitter glutamic acid, the study adds further support to the hypothesis that L-glutamate is the neurotransmitter released by baroreceptor afferent nerves.

Topics: Acute Disease; Animals; Ascorbic Acid; Blood Pressure; Heart Rate; Hypertension; Kainic Acid; Male; Medulla Oblongata; Procaine; Pyrrolidines; Rats

The aims of follow up of patients with bronchial carcinoma are: 1. Complete use of all therapeutical possibilities. 2. Avoidance of preventable complications of therapeutical prescriptions. 3. Prevention of sicknesses beside the basic complaint. 4. The rehabilitation of the patient. The medical structure for realizing these aims, we suppose in the cooperation of the doctor of the family or the factory, who will see the patient in intervals of four weeks, and the ambulant working pulmologist, who will see the patient in intervals of 3 months, and the thorax-centre, what the patient will consult once or twice the year, and the centre for rehabilitation, where patients with limited cardiorespiratoric function will get an appropriated training of condition. Two cure-places with this special direction will satisfy the require in the GDR. The oncologist of the district where the patient lives will be the coordinator of all parts of this system and the controller to keep its function. The effectivity of follow up will be realised by clear and proofed recommendations by the therapeutical centres and the continued consultations on actual problem cases with the shared doctors. The data processing can do an useful help in this cooperation.

Topics: Aftercare; Ascorbic Acid; Bronchial Neoplasms; Germany, East; Humans; Hypertension; Legislation, Medical; Neoplasm Metastasis; Physical Therapy Modalities; Work Capacity Evaluation

Biochemical studies on large groups of apparently healthy women taking oral contraceptives are intended to find which organs and tissues are most stressed, in the hope than an indication of clinical side effects will result. If contraceptive steroid dose is reduced, the incidence of systemic side effects decreases and this correlates well with the decreased abnormality of many metabolic and biochemical parameters. Reduction of dosage has an equivocal effect on gynaecological side affects-some increase, some decrease. An account is given of the possible relationship between clinical side effects of oral contraceptives, and dose-related changes in plasma proteins, vitamin status and tissue enzymes.

Topics: Ascorbic Acid; Contraceptives, Oral; Contraceptives, Oral, Synthetic; Dose-Response Relationship, Drug; Headache; Humans; Hypertension; Libido; Male; Monoamine Oxidase; Prolactin; Pyridoxine; Receptors, Estrogen; Sex Hormone-Binding Globulin; Thiamine

Topics: Animals; Arachidonic Acids; Ascorbic Acid; Blood Pressure; Catecholamines; Desoxycorticosterone; Dextroamphetamine; Hypertension; Kidney; Male; Nephrectomy; Rats; Sodium Chloride; Time Factors; Tyrosine

Topics: Adult; Aged; Arteriosclerosis; Ascorbic Acid; Cadmium; Cholesterol; Deficiency Diseases; Female; Humans; Hypertension; Male; Middle Aged; Smoking

Topics: Actins; Actomyosin; Adenosine Triphosphatases; Adenosine Triphosphate; Animals; Arteries; Ascorbic Acid; Calcium; Carotid Arteries; Cattle; Chemical Precipitation; Hypertension; In Vitro Techniques; Magnesium; Microscopy, Electron; Muscle Contraction; Muscle Proteins; Myosins; Potassium Chloride; Sodium Chloride; Spectrophotometry; Viscosity

Topics: Ascorbic Acid; Aspirin; Asthma; Calcium; Citrates; Coronary Disease; Depression, Chemical; Diabetes Mellitus; Duodenal Ulcer; Dwarfism, Pituitary; Emphysema; Facial Paralysis; Gluconates; Histamine H1 Antagonists; Humans; Hypertension; Hyperthyroidism; Kidney Calculi; Liver Diseases, Parasitic; Magnesium; Oxalates; Phosphates; Pyridoxine; Schistosomiasis; Stimulation, Chemical; Terpenes; Tuberculosis, Pulmonary

Topics: Adenosine Triphosphate; Animals; Antihypertensive Agents; Ascorbic Acid; Drug Synergism; Folic Acid; Hypertension; Male; Rats; Tyrosine

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Chronic Disease; Female; Fibrinolysis; Hematologic Diseases; Humans; Hypertension; Male; Middle Aged; Nephritis

Topics: Acetylcholine; Adrenal Glands; Adrenal Medulla; Animals; Aortic Valve Insufficiency; Ascorbic Acid; Cardiomegaly; Catecholamines; Corticosterone; Heart; Heart Failure; Hypertension; Myocardium; Norepinephrine; Organ Size; Rabbits

Topics: Ascorbic Acid; Aspirin; Epistaxis; Humans; Hypertension; Hypnotics and Sedatives; Hypotension, Controlled; Meperidine

Topics: Aged; Angiomatosis; Arteriosclerosis; Ascorbic Acid; Glomerulonephritis; Humans; Hypertension; Keratosis; Male; Nails; Pressure; Purpura

Topics: Ambulatory Care; Ascorbic Acid; Humans; Hypertension

Topics: Adolescent; Adult; Ascorbic Acid; Flavonoids; Heart Conduction System; Humans; Hypertension

Topics: Aesculus; Ascorbic Acid; Brain Edema; Capillary Permeability; Drug Therapy; Fagaceae; Flavones; Flavonoids; Hemorrhagic Disorders; Humans; Hypertension; Intracranial Arteriosclerosis; Rutin

Topics: 17-Hydroxycorticosteroids; Adolescent; Adrenal Cortex Hormones; Adrenal Gland Diseases; Adrenocorticotropic Hormone; Adult; Aged; Ascorbic Acid; Brain Diseases; Brain Neoplasms; Female; Humans; Hypertension; In Vitro Techniques; Male; Middle Aged; Pituitary Diseases; Thyroid Diseases; Urine

Topics: Arteriosclerosis; Ascorbic Acid; Cholesterol; Coronary Vessels; Humans; Hypercholesterolemia; Hypertension; Hypertension, Renal; Kidney; Vitamins

Topics: Ascorbic Acid; Bendroflumethiazide; Diuretics; Edema, Cardiac; Electrolytes; Feeding and Eating Disorders; Geriatrics; Heart Failure; Humans; Hypertension; Nausea; Potassium; Toxicology; Vitamin B Complex; Vomiting

Topics: Addison Disease; Adrenal Insufficiency; Ascorbic Acid; Cortisone; Desoxycorticosterone; Dexamethasone; Drug Therapy; Geriatrics; Hypertension; Hypoadrenocorticism, Familial; Menopause; Nephritis; Prednisone; Triamcinolone

Topics: Arteriosclerosis; Ascorbic Acid; Blood Chemical Analysis; Cardiovascular Diseases; Coronary Disease; Geriatrics; Heart Failure; Humans; Hypertension

Topics: Adrenal Cortex; Adrenal Glands; Ascorbic Acid; Desoxycorticosterone; Guanethidine; Hypertension; Pharmacology; Rats; Research

Topics: Adrenal Glands; Angiotensin II; Ascorbic Acid; Humans; Hypertension

Topics: Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Essential Hypertension; Humans; Hypertension; Lipids

Topics: Acid-Base Equilibrium; Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Cholesterol; Humans; Hypertension; Vitamins

Topics: Animals; Ascorbic Acid; Choline; Diet; Hypertension; Rats; Riboflavin; Sodium Chloride; Vitamins

Topics: Ascorbic Acid; Female; Humans; Hypertension; Magnesium Sulfate; Pre-Eclampsia; Pregnancy; Testosterone; Thiamine Pyrophosphate; Vitamins

Topics: Adrenocorticotropic Hormone; Ascorbic Acid; Cortisone; Desoxycorticosterone; Desoxycorticosterone Acetate; Hypertension; Vitamins

Topics: Adrenal Glands; Adrenalectomy; Ascorbic Acid; Cortisone; Desoxycorticosterone; Desoxycorticosterone Acetate; Hypertension; Vitamins

Topics: Ascorbic Acid; Blood Pressure; Blood Pressure Determination; Epinephrine; Humans; Hypertension

Topics: Animals; Ascorbic Acid; Hypertension; Kidney; Pituitary Gland; Rats; Vitamins

Topics: Ascorbic Acid; Humans; Hypertension; Nephritis

Topics: Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Blood; Cholesterol; Humans; Hypertension; Vitamins

Topics: Animals; Ascorbic Acid; Folic Acid; Hemodynamics; Hypertension; Rats

Topics: Ascorbic Acid; Blood Pressure; Blood Pressure Determination; Calcium; Calcium Chloride; Capillary Fragility; Humans; Hypertension; Vitamins

Topics: Adrenal Cortex Hormones; Ascorbic Acid; Blood Pressure; Blood Pressure Determination; Desoxycorticosterone Acetate; Hypertension; Vitamins

Topics: Ascorbic Acid; Blood Pressure; Blood Pressure Determination; Carcinoma; Humans; Hypertension; Vitamins