cholecalciferol and Hypertension

Previous randomized clinical trials (RCTs) of the effects of vitamin D3 supplementation (VD3S) on blood pressure have generated inconsistent results. We evaluated the effect of VD3S on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in a meta-analysis.. Literature searches of PubMed, Scopus, Ovid, and Google scholar for publications in English were conducted up to April 2015. RCTs that assessed the effect of VD3S on SBP and DBP were selected.. A total of 30 RCTs with 41 arms including 4744 participants were included. The mean duration of the studies was 5.6 ± 4.0 months, and doses of VD3S varied between 200 and 12,000 IU/day. VD3S had no effect on SBP (-0.68 mmHg, 95%CI: -2.19 to 0.84), and DBP (-0.57 mmHg, 95%CI: -1.36 to 0.22). Subgroup analysis revealed that daily vitamin D3 therapy at a dose of >800 IU/day for <6 months in subjects ≥50 years old reduced both SBP and DBP (p < 0.001). In addition, VD3S showed hypotensive effects in healthy subjects and hypertensive patients, but a hypertensive effect in overweight and obese subjects. However, after excluding overweight and obese subjects, VD3S significantly reduced SBP and DBP. VD3S in combination with calcium supplementation significantly elevated SBP (3.64 mmHg, 95%CI: 3.15-4.13) and DBP (1.71 mmHg, 95%CI: 1.25-2.18). No evidence of publication bias was found. The effects of VD3S on blood pressure depend on dose of supplementation, treatment regimens, trial duration, and population subgroup. Supplementation may be beneficial at daily doses >800 IU/day for <6 months in subjects ≥50 years old.

Topics: Blood Pressure; Calcium; Cholecalciferol; Dietary Supplements; Dose-Response Relationship, Drug; Female; Humans; Hypertension; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Treatment Outcome; Vitamin D Deficiency

Calcium regulates majority of metabolic processes within human organism and its optimal intake decreases risk of metabolic illnesses conditioned by diet. Deficiency of calcium results in higher body max index, increase risk of insulin resistance, diabetes type 2 and osteoporosis. Diet delivering full calcium load diminished impendency of hypertension; calcium regulates tension of smooth muscles of blood vessels, limits neurotransmitters activity and also diminish hazardous activity of sodium chloride. Anticancerogenic activity of calcium results from formation insoluble bile acids and fat acids salts, and most of all, from inhibition of intestine mucosa cells hyper proliferation. Due to presence of vitamin D3, CLA, proteins and bioactive peptides emerging from them, milk is more efficient in prophylaxis of diet conditioned illnesses than calcium supplements. Efficiency of milk and dairy products in treatment of obesity, sclerosis and hypertension has been proved by DASH diet.

Topics: Animals; Calcium, Dietary; Cholecalciferol; Dairy Products; Humans; Hypertension; Intestinal Mucosa; Milk; Muscle, Smooth; Neoplasms; Obesity; Synaptic Transmission

Atherosclerosis is common in patients with chronic kidney disease (CKD), and cardiovascular disease (CVD) represents a major cause of death in these patients, especially, in patients with end-stage renal disease(ESRD). The pathological features in ESRD patients are intimal atherosclerosis and medial calcific sclerosis. The important risk factors for CVD in ESRD patients are hypertension, dyslipidemia and CKD bone and mineral disorder (CKD-MBD). Atherosclerosis has been evaluated by measurements of intima-media thickness and pulse-wave velocity. Although the target blood pressure still undetermined, hypertension would be treated with renin-angiotensin system inhibitors. In addition, treatment of dyslipidemia with statins may lead to favorable CVD outcome. Finally, inhibition of vascular calcification should be important by treatment with active vitamin D and sevelamer.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Atherosclerosis; Bone Diseases, Metabolic; Calcinosis; Cholecalciferol; Chronic Disease; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Kidney Failure, Chronic; Polyamines; Risk Factors; Sevelamer; Tunica Intima; Vascular Diseases

Current evidence indicates that vitamin D3 plays significant role in calcium balance and bone metabolism through lifetime. There are also evidence on preventive efficacy of vitamin D3 in diabetes, insulin-resistance, hypertension and malignancy.. The aim of the systematic review was to gather evidence regarding vitamin D3 in prevention of diseases in adults. MEDLINE via Pubmed was searched using key words: "vitamin D3, "prevention", "adults", "cardiovascular diseases", cancer", "osteoporosis", "common cold", "cold", "diabetes", "obesity", "depression". 26 trials were included into analysis: 17 randomized clinical trials, five observational studies, two systematic reviews, and two metaanalysis.. Vitamin D3 appears to has beneficial effect in depression therapy, protective effect on beta-cells in diabetic patients and reducing frequency of adverse events such as thrombosis in patients with prostate cancer. Supplementing with vitamin D3 results with no significant improve in reducing body weight, fat, blood pressure, risk of hypertension, level of lipids in serum, response to treatment in cancer prostate (together with dexamethasone and carboplatin). Many studies highlights beneficial influence of vitamin D3 with calcium on bone mineral density in whole body. Another studies show improve in bone mineral density in hips and pelvic bones only. There were inconsistencies of studies results regarding role of vitamin D3 in prevention of diabetes, risk of breast cancer and influence on bone mineral density.. Despite all inconsistencies supplementation of vitamin D3 is important and plays role in effective osteoporotic management and there is evidence on preventive efficacy of vitamin D3 in different diseases.

Topics: Adult; Bone Density; Calcium; Cardiovascular Diseases; Cholecalciferol; Diabetes Mellitus; Dietary Supplements; Humans; Hypertension; Neoplasms; Osteoporosis; Thrombosis

Low dietary intake of calcium stimulates the activation of vitamin D3 precursors to calcitriol in the kidney. This circulating hormone raises blood and urinary calcium by increasing both gastrointestinal absorption of calcium and bone resorption. Renal activation of vitamin D3 is under tight feedback control. Macrophages also activate vitamin D3, but, unlike renal tubular cells, they lack feedback suppression of the activating 1alpha-hydroxylase. In large-scale epidemiologic studies, blood pressure correlated positively with serum and urinary calcium but inversely with the dietary intake of calcium. Several population-based reports, including the Framingham Study, noticed an association of carotid plaques, arterial calcification, and increased arterial stiffness with lower bone-mineral content. Randomized clinical trials of calcium supplementation did not demonstrate a consistent effect on blood pressure. Macrophages in atherosclerotic lesions can locally activate vitamin D3 to calcitriol, which might contribute to arterial stiffening and hypertension. Calcitriol acts as a vasoactive and pro-oxidative substance on vascular smooth muscle cells. In animal models, active vitamin D3 promotes arterial stiffening and the pathogenesis of systolic hypertension and perpetuates a self-sustaining cycle leading to arterial damage and calcification. On the other hand, active vitamin D3 inhibits renin activity, thereby decreasing blood pressure in short-term, randomized trials. This article assesses the potential role of active vitamin D3 in causing cardiovascular complications via its effects on the structure of the arterial wall and the pathogenesis of hypertension. To set the stage and open up new perspectives, our article also summarizes the pathways leading to the renal and extrarenal activation and metabolism of vitamin D3 and will propose some directions for further research in this complex field.

Topics: Animals; Arteries; Atherosclerosis; Cholecalciferol; Elasticity; Humans; Hypertension; Kidney; Muscle, Smooth, Vascular

The basic function of vitamin D3 in human body is to maintain the calcium-phosphate homeostasis. Its metabolic function is mediated by the nuclear VDR receptor. The existance of vitamin D3 receptors outside tissues and organs which take part in calcium-phosphate metabolism has resulted in not treating it as an anti rickets agent only. Lower arterial blood pressure observed in people living in sunny areas and decrease of arterial blood pressure values after exposure to UVB radiation could confirm the relationship between vitamin D3 and hypertension. Perhaps through its influence on calcium-phosphate metabolism, RAA system, immune system, control of endocrine glands and endothelium function the vitamin D3 contributes to lowering arterial blood pressure and lessening the risk of cardiovascular disease.

Topics: Blood Pressure; Calcium; Cholecalciferol; Humans; Hypertension; Phosphorus; Renin-Angiotensin System

Vitamin D3 plays a key role in regulating calcium and mineral homeostasis in support of normal development and maintenance of bone. The classic effects of vitamin D3 include promoting absorption of dietary calcium in the gut and, through its actions as a steroid endocrine hormone, regulating the synthesis and secretion of parathyroid hormone. The effects of the vitamin D3 system are mediated through the highly regulated generation of the potent, active metabolite 1,25-dihydroxyvitamin D3 (calcitriol). Vitamin D3 exerts its effects through the vitamin D3 receptor (VDR), a ligand-activated nuclear receptor expressed in a wide array of tissue and cell types. Studies performed in mice rendered deficient for VDR suggest that calcitriol and VDR may inhibit the renin-angiotensin system and reduce blood pressure in the long-term. Clinical studies suggest that administration of vitamin D3 analogs produces differential benefit with regards to mortality in dialysis patients; other studies suggest that vitamin D3 analogs may provide cardiovascular benefit in both dialysis and nondialysis patients. This paper reviews clinical and preclinical studies, which suggest that vitamin D3 analogs may provide therapeutic utility in the treatment of cardiovascular disease independent of those mechanisms typically associated with the vitamin D3 endocrine system.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Cholecalciferol; Clinical Trials as Topic; Heart Failure; Humans; Hypertension; Parathyroid Hormone

Topics: Animals; Base Sequence; Blood Pressure; Cholecalciferol; DNA; Enhancer Elements, Genetic; Gene Expression Regulation; Humans; Hypertension; Mice; Molecular Sequence Data; Receptors, Calcitriol; Renin; Renin-Angiotensin System

Pronounced vascular calcium overload, especially of compliance arteries, is an important aspect of aging, and of various age-related vascular diseases such as hypertension and atherosclerosis. The development of new drugs specifically aimed at attenuating the evolution and/or pathological consequences of vascular calcium overload is hindered by the paucity of animal models available. Although several laboratory animals exhibit vascular calcium overload, this evolves slowly and is far less marked than in man. Nevertheless, Fleckenstein and associates (1989) suggested a suitable animal model involving the treatment of young rats with vitamin D3 and nicotine; such treatment produces pronounced vascular calcium overload within a few weeks. This paper describes the cardiovascular effects of such treatment, and our preliminary attempts to pharmacologically modify vascular calcium overload and its cardiovascular consequences.

Topics: Animals; Arteriosclerosis; Blood Vessels; Calcium; Cholecalciferol; Hemodynamics; Hypertension; Nicotine; Rats; Tissue Distribution

Accumulating evidence suggests that potential cardiovascular benefits of vitamin D supplementation may be restricted to individuals with very low 25-hydroxyvitamin D (25(OH)D) concentrations; the effect of vitamin D on blood pressure (BP) remains unclear. We addressed this issue in a post hoc analysis of the double-blind, randomized, placebo-controlled Styrian Vitamin D Hypertension Trial (2011−2014) with 200 hypertensive patients with 25(OH)D levels <30 ng/mL. We evaluated whether 2800 IU of vitamin D3/day or placebo (1:1) for 8 weeks affects 24-hour systolic ambulatory BP in patients with 25(OH)D concentrations <20 ng/mL, <16 ng/mL, and <12 ng/mL and whether achieved 25(OH)D concentrations were associated with BP measures. Taking into account correction for multiple testing, p values < 0.0026 were considered significant. No significant treatment effects on 24-hour BP were observed when different baseline 25(OH)D thresholds were used (all p-values > 0.30). However, there was a marginally significant trend towards an inverse association between the achieved 25(OH)D level with 24-hour systolic BP (−0.196 per ng/mL 25(OH)D, 95% CI (−0.325 to −0.067); p = 0.003). In conclusion, we could not document the antihypertensive effects of vitamin D in vitamin D-deficient individuals, but the association between achieved 25(OH)D concentrations and BP warrants further investigations on cardiovascular benefits of vitamin D in severe vitamin D deficiency.

Topics: Blood Pressure; Calcifediol; Cholecalciferol; Dietary Supplements; Double-Blind Method; Humans; Hypertension; Vitamin D; Vitamin D Deficiency; Vitamins

The vitamin D and microRNA (miR) systems may play a role in the pathogenesis of cardiometabolic disorders, including hypertension. The HYPODD study was a double-blind placebo-controlled trial aiming to assess the effects of cholecalciferol treatment in patients with well-controlled hypertension and hypovitaminosis D (25OHD levels < 50 nmol/L). In addition to this clinical trial, we also evaluated the effects of cholecalciferol and calcitriol treatment on miR-21 expression in vivo and in vitro, respectively. Changes in the cardiovascular risk profiles were evaluated in HYPODD patients treated with cholecalciferol (C-cohort) or with placebo (P-cohort). The miR-21circulating levels were measured in four C-cohort patients and five P-cohort patients. In vitro, the miR-21 levels were measured in HEK-293 cells treated with calcitriol or with ethanol vehicle control. Cholecalciferol treatment increased 25OHD levels and reduced parathormone, total cholesterol, and low-density lipoprotein cholesterol levels in C-cohort patients, whereas no significant changes in these parameters were observed in P-cohort patients. The miR-21 circulating levels did not change in the C- or the P-cohort patients upon treatment. Calcitriol treatment did not affect miR-21 levels in HEK-293 cells. In conclusion, hypovitaminosis D correction ameliorated the cardiovascular risk profiles in hypertensive patients treated with cholecalciferol but did not influence the miR-21 expression.

Topics: Calcitriol; Cardiovascular Diseases; Cholecalciferol; Cholesterol; Dietary Supplements; Double-Blind Method; Heart Disease Risk Factors; HEK293 Cells; Humans; Hypertension; MicroRNAs; Risk Factors; Vitamin D; Vitamin D Deficiency; Vitamins

Animal and cell models indicated that vitamin D modulates inflammatory activity, which is considered relevant in the pathogenesis of arterial hypertension and cardiovascular diseases. We therefore aimed to investigate the effect of vitamin D supplementation on systemic markers of inflammation in a cohort of hypertensive patients.. Vitamin D. ClinicalTrials.gov Identifier: NCT02136771; EudraCT No. 2009-018,125-70. Start Date: 2011-04-06.

Topics: Aged; Austria; Biomarkers; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Hypertension; Inflammation Mediators; Male; Middle Aged; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency; Vitamins

The benefits of vitamin D, omega-3 fatty acids, and exercise in disease prevention remain unclear.. To test whether vitamin D, omega-3s, and a strength-training exercise program, alone or in combination, improved 6 health outcomes among older adults.. Double-blind, placebo-controlled, 2 × 2 × 2 factorial randomized clinical trial among 2157 adults aged 70 years or older who had no major health events in the 5 years prior to enrollment and had sufficient mobility and good cognitive status. Patients were recruited between December 2012 and November 2014, and final follow-up was in November 2017.. Participants were randomized to 3 years of intervention in 1 of the following 8 groups: 2000 IU/d of vitamin D3, 1 g/d of omega-3s, and a strength-training exercise program (n = 264); vitamin D3 and omega-3s (n = 265); vitamin D3 and exercise (n = 275); vitamin D3 alone (n = 272); omega-3s and exercise (n = 275); omega-3s alone (n = 269); exercise alone (n = 267); or placebo (n = 270).. The 6 primary outcomes were change in systolic and diastolic blood pressure (BP), Short Physical Performance Battery (SPPB), Montreal Cognitive Assessment (MoCA), and incidence rates (IRs) of nonvertebral fractures and infections over 3 years. Based on multiple comparisons of 6 primary end points, 99% confidence intervals are presented and P < .01 was required for statistical significance.. Among 2157 randomized participants (mean age, 74.9 years; 61.7% women), 1900 (88%) completed the study. Median follow-up was 2.99 years. Overall, there were no statistically significant benefits of any intervention individually or in combination for the 6 end points at 3 years. For instance, the differences in mean change in systolic BP with vitamin D vs no vitamin D and with omega-3s vs no omega-3s were both -0.8 (99% CI, -2.1 to 0.5) mm Hg, with P < .13 and P < .11, respectively; the difference in mean change in diastolic BP with omega-3s vs no omega-3s was -0.5 (99% CI, -1.2 to 0.2) mm Hg; P = .06); and the difference in mean change in IR of infections with omega-3s vs no omega-3s was -0.13 (99% CI, -0.23 to -0.03), with an IR ratio of 0.89 (99% CI, 0.78-1.01; P = .02). No effects were found on the outcomes of SPPB, MoCA, and incidence of nonvertebral fractures). A total of 25 deaths were reported, with similar numbers in all treatment groups.. Among adults without major comorbidities aged 70 years or older, treatment with vitamin D3, omega-3s, or a strength-training exercise program did not result in statistically significant differences in improvement in systolic or diastolic blood pressure, nonvertebral fractures, physical performance, infection rates, or cognitive function. These findings do not support the effectiveness of these 3 interventions for these clinical outcomes.. ClinicalTrials.gov Identifier: NCT01745263.

Topics: Aged; Aged, 80 and over; Cholecalciferol; Cognition Disorders; Dietary Supplements; Double-Blind Method; Fatty Acids, Omega-3; Female; Follow-Up Studies; Fractures, Bone; Health Status; Humans; Hypertension; Immunity; Male; Physical Fitness; Resistance Training; Treatment Outcome; Vitamins

Observational and experimental data reinforce the concept that vitamin D is associated with the pathogenesis of arterial hypertension. We investigated the effect of a single dose of 100,000 IU of cholecalciferol, in office blood pressure (BP), and 24-h ambulatory blood pressure monitoring (ABPM) in patients with type 2 diabetes mellitus (DM), hypertension, and hypovitaminosis D. Forty-three patients were randomized to a placebo or cholecalciferol group. BP was assessed by office measurements and 24-h ABPM, before and after intervention. At week 8, a greater decrease in median ABPM values was observed in cholecalciferol supplementation than in the placebo group for systolic 24-h (- 7.5 vs. - 1; P = 0.02), systolic daytime (- 7 vs. - 1; P = 0.007), systolic nighttime (- 7.0 vs. 3; P = 0.009), diastolic 24-h (- 3.5 vs. - 1; P = 0.037), and daytime DBP (- 5 vs. 0; P = 0.01). Office DBP was also reduced after vitamin D supplementation. A single dose of vitamin D

Topics: Aged; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cholecalciferol; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Treatment Outcome; Vitamin D Deficiency

Cardiovascular Disease (CVD) and related disorders remain a leading cause of health disparities and premature death for African Americans. Hypovitaminosis D is disproportionately prevalent in African Americans and has been linked to CVD and CVD risk factors including hypertension, diabetes and obesity. Thus, hypovitaminosis D may represent a common pathway influencing CV risk factors in a select subgroup of persons. The purpose of this paper is to report the study design of a prospective eight week prospective double-blind randomized, placebo-controlled trial (n = 330 allocated 2:1 to intervention vs. control) to assess the effect of placebo vs. high-dose oral cholecalciferol (100,000 IU vitamin D3 at baseline and week 2) on 6-week change of select biologic cardiometabolic risk factors (including parathyroid hormone to assess biologic activity, pro-inflammatory/pro-thrombotic/fibrotic markers, insulin sensitivity and vitamin D metabolites) and their relationship to vitamin D administration and modification by vitamin D receptor polymorphisms in overweight, hypertensive African Americans with hypovitaminosis D. Findings from this trial will present insights into potential causal links between vitamin D repletion and mechanistic pathways of CV disease, including established and novel genomic markers.

Topics: Black or African American; Cholecalciferol; Cytokines; Double-Blind Method; Humans; Hypertension; Inflammation; Insulin Resistance; Overweight; Parathyroid Hormone; Vitamin D Deficiency; Vitamin D-Binding Protein; Vitamins

Accumulating evidence has proposed a correlation between vitamin D (25(OH)D) insufficiency and cardiovascular (CV) disease. Vitamin D associated effects on endothelial function have been suggested to be a possible culprit. The present study investigated the association of vitamin D3 treatment on markers of endothelial dysfunction in patients with arterial hypertension.. The Styrian Vitamin D Hypertension Trial is a double-blind, placebo-controlled, single-centre study conducted at the Medical University of Graz, Austria. A total of 200 study participants with arterial hypertension and 25(OH)D levels below 30ng/mL were enrolled. The study participants were randomized to receive 2800 IU of vitamin D3 per day as oily drops (n=100) or placebo (n=100) for a duration of eight weeks. The present study uses an analysis of covariance (ANCOVA) to investigate the effect of vitamin D3 treatment on symmetric (SDMA) and asymmetric dimethylarginine (ADMA). A total of 187 participants (mean [SD] age 60.0 [11.3] years; 47% women; 25(OH)D 21.2 [5.6]ng/mL; mean systolic blood pressure of 131.4 [8.9] mmHg on a median of 2 antihypertensive drugs) completed the trial. Mean treatment effect was -0.004 (95%CI [-0.03 to 0.04]; P=0.819) on ADMA and 0.001 (95%CI [-0.05 to 0.05]; P=0.850) on SDMA. In the subgroup analysis patients with a 25(OH)D concentration <20ng/mL had a significant increase in their log l-arginine/ADMA ratio (mean treatment effect 18.4 95%CI [1.84-34.9]μmol/L/μmol/L; P=0.030). ClinicalTrials.gov Identifier: NCT02136771 EudraCT number: 2009-018125-70 CONCLUSIONS: Vitamin D3 supplementation in hypertensive patients with low 25-hydroxyvitamin D has no significant effect on ADMA and SDMA.

Topics: Aged; Analysis of Variance; Arginine; Blood Pressure; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Vitamin D; Vitamin D Deficiency

Cohort studies have reported increased incidence of cardiovascular disease (CVD) among individuals with low vitamin D status. To date, randomized clinical trials of vitamin D supplementation have not found an effect, possibly because of using too low a dose of vitamin D.. To examine whether monthly high-dose vitamin D supplementation prevents CVD in the general population.. The Vitamin D Assessment Study is a randomized, double-blind, placebo-controlled trial that recruited participants mostly from family practices in Auckland, New Zealand, from April 5, 2011, through November 6, 2012, with follow-up until July 2015. Participants were community-resident adults aged 50 to 84 years. Of 47 905 adults invited from family practices and 163 from community groups, 5110 participants were randomized to receive vitamin D3 (n = 2558) or placebo (n = 2552). Two participants retracted consent, and all others (n = 5108) were included in the primary analysis.. Oral vitamin D3 in an initial dose of 200 000 IU, followed a month later by monthly doses of 100 000 IU, or placebo for a median of 3.3 years (range, 2.5-4.2 years).. The primary outcome was the number of participants with incident CVD and death, including a prespecified subgroup analysis in participants with vitamin D deficiency (baseline deseasonalized 25-hydroxyvitamin D [25(OH)D] levels <20 ng/mL). Secondary outcomes were myocardial infarction, angina, heart failure, hypertension, arrhythmias, arteriosclerosis, stroke, and venous thrombosis.. Of the 5108 participants included in the analysis, the mean (SD) age was 65.9 (8.3) years, 2969 (58.1%) were male, and 4253 (83.3%) were of European or other ethnicity, with the remainder being Polynesian or South Asian. Mean (SD) baseline deseasonalized 25(OH)D concentration was 26.5 (9.0) ng/mL, with 1270 participants (24.9%) being vitamin D deficient. In a random sample of 438 participants, the mean follow-up 25(OH)D level was greater than 20 ng/mL higher in the vitamin D group than in the placebo group. The primary outcome of CVD occurred in 303 participants (11.8%) in the vitamin D group and 293 participants (11.5%) in the placebo group, yielding an adjusted hazard ratio of 1.02 (95% CI, 0.87-1.20). Similar results were seen for participants with baseline vitamin D deficiency and for secondary outcomes.. Monthly high-dose vitamin D supplementation does not prevent CVD. This result does not support the use of monthly vitamin D supplementation for this purpose. The effects of daily or weekly dosing require further study.. clinicaltrials.gov Identifier: ACTRN12611000402943.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Arrhythmias, Cardiac; Arteriosclerosis; Cardiovascular Diseases; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; New Zealand; Proportional Hazards Models; Stroke; Venous Thrombosis; Vitamin D Deficiency; Vitamins

Although studies have linked vitamin D deficiency with immune-mediated diseases, data demonstrating a direct effect on T-cell function are sparse.. Our objective was to determine whether oral vitamin D3 influences T-cell activation in humans with vitamin D deficiency.. This was a single-center ancillary study within Vitamin D Therapy in Individuals at High Risk of Hypertension, a double-blind, multicenter, randomized controlled trial.. This study was undertaken in a single academic medical center.. Adults with vitamin D deficiency and untreated pre- or early stage I hypertension were included.. In Vitamin D Therapy in Individuals at High Risk of Hypertension, participants were randomized to either low- (400 IU daily) or high- (4000 IU daily) dose oral vitamin D3 for 6 months. In this ancillary study of 38 patients, we measured CD4+ T-cell activation estimated by intracellular ATP release after stimulation of whole blood with plant lectin phytohemagglutinin collected at baseline (pretreatment) and 2-month follow-up.. Determining whether ATP level changes were significantly different between treatment groups was the main outcome measure.. Treatment with 4000 IU of vitamin D3 decreased intracellular CD4+ ATP release by 95.5 ng/ml (interquartile range, -219.5 to 105.8). In contrast, 400 IU of vitamin D3 decreased intracellular CD4+ ATP release by 0.5 ng/ml (interquartile range, -69.2 to 148.5). In a proportional odds model, high-dose vitamin D3 was more likely than low-dose vitamin D3 to decrease CD4+ ATP release (odds ratio, 3.43; 95% confidence interval, 1.06-1.11).. In this ancillary study of a randomized controlled trial, we found that high-dose vitamin D3 significantly reduced CD4+ T-cell activation compared to low-dose vitamin D3, providing human evidence that vitamin D can influence cell-mediated immunity.

Topics: Adenosine Triphosphate; Adult; Cholecalciferol; Cohort Studies; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypertension; Lymphocyte Activation; Male; Middle Aged; T-Lymphocytes; Vitamin D Deficiency; Vitamins

A large body of epidemiological and experimental evidence suggests that vitamin D deficiency may promote hypertension. This raises the possibility that vitamin D supplementation could be a simple intervention to reduce blood pressure, but data from prospective, randomized trials are limited.. A double-blind, randomized, controlled trial was conducted at 4 sites in the United States. We enrolled 534 individuals 18 to 50 years of age with low vitamin D status (25-hydroxyvitamin D levels ≤25 ng/mL) and systolic blood pressure of 120 to 159 mm Hg. Participants were randomized to high-dose (4000 IU/d) versus low-dose (400 IU/d) oral vitamin D3 for 6 months. The primary end point was change in mean 24-hour systolic blood pressure. Secondary end points included change in ambulatory diastolic blood pressure and clinic systolic and diastolic blood pressures. The median age was 38 years, and 62% of participants were men. Forty-six percent of participants were white, and 48% were black. The median 25-hydroxyvitamin D level at baseline was 15.3 ng/mL. Four-hundred fifty-five participants (85%) had at least 1 follow-up blood pressure measurement; 383 participants (72%) completed the full 6-month study. At the end of the study, there was no significant difference in the primary end point (change in mean 24-hour systolic blood pressure, -0.8 versus -1.6 mm Hg in the high-dose and low-dose arms; P=0.71) or in any of the secondary end points. Furthermore, there was no evidence of association between change in 25-hydroxyvitamin D and change in 24-hour systolic blood pressure at 6 months (Spearman correlation coefficient, -0.05, P=0.34). Results were consistent across prespecified subgroups.. Vitamin D supplementation did not reduce blood pressure in individuals with prehypertension or stage I hypertension and vitamin D deficiency. Our findings suggest that the association between vitamin D status and elevated blood pressure noted in observational studies is not causal.. http://www.clinicaltrials.gov. Unique identifier: NCT01240512.

Topics: Adult; Blood Pressure; Cholecalciferol; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Prehypertension; Vitamin D Deficiency

At this time, good quality randomized clinical trials assessing the effects of vitamin D supplementation on cardiometabolic outcomes are lacking in the international literature.. To fill this gap, the Working Group on Vitamin D and Cardiorenal Disorders established jointly by the Italian Society of Hypertension (SIIA) and the Forum in Bone and Mineral Research conceived the HYPODD study (HYPOvitaminosis D and organ Damage).. HYPODD is a no-profit multicenter 12-month parallel-group double-blind placebo controlled randomized trial aiming to assess the effects of cholecalciferol supplementation on blood pressure control, antihypertensive drugs consumption and progression of target organ damage in patients with essential hypertension and 25-hydroxyvitamin D serum level lower than 20 ng/ml (vitamin D deficiency). HYPODD is coordinated by the European Society Excellence Center of Hypertension of Federico II University, Naples, and involves 12 academic institutions in Italy (Ancona, Milan, Padua, Perugia, Rome, Siena, Trieste, Turin, Udine, Varese, and Verona).. The HYPODD study has been registered at the Agenzia Italiana del Farmaco-Osservatorio sulla Sperimentazione Clinica del Farmaco (AIFA-OsSC) and EUDRACT sites (n° 2012-003514-14) and has been approved by the Ethical Committees of all the Centers involved in the study. The patients' recruitment is currently underway.

Topics: Antihypertensive Agents; Arterial Pressure; Biomarkers; Cholecalciferol; Clinical Protocols; Dietary Supplements; Disease Progression; Double-Blind Method; Humans; Hypertension; Italy; Patient Selection; Sample Size; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Blacks have significantly higher rates of hypertension than whites, and lower circulating levels of 25-hydroxyvitamin D. There are few data about the effect of vitamin D3 (cholecalciferol) supplementation on blood pressure in blacks. During 2 winters from 2008 to 2010, 283 blacks (median age, 51 years) were randomized into a 4-arm, double-blind trial for 3 months of placebo, 1000, 2000, or 4000 international units of cholecalciferol per day. At baseline, 3 months, and 6 months, systolic and diastolic pressure and 25-hydroxyvitamin D were measured. The 3-month follow-up was completed in 250 (88%) participants. The difference in systolic pressure between baseline and 3 months was +1.7 mm Hg for those receiving placebo, -0.66 mm Hg for 1000 U/d, -3.4 mm Hg for 2000 U/d, and -4.0 mm Hg for 4000 U/d of cholecalciferol (-1.4 mm Hg for each additional 1000 U/d of cholecalciferol; P=0.04). For each 1-ng/mL increase in plasma 25-hydroxyvitamin D, there was a significant 0.2-mm Hg reduction in systolic pressure (P=0.02). There was no effect of cholecalciferol supplementation on diastolic pressure (P=0.37). Within an unselected population of blacks, 3 months of oral vitamin D3 supplementation significantly, yet modestly, lowered systolic pressure. Future trials of vitamin D supplementation on blood pressure are needed to confirm these promising results, particularly among blacks, a population for whom vitamin D deficiency may play a more specific mechanistic role in the pathogenesis of hypertension.

Topics: Administration, Oral; Black or African American; Blood Pressure; Cholecalciferol; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Follow-Up Studies; Humans; Hypertension; Massachusetts; Prevalence; Prospective Studies; Treatment Outcome; Vitamins

Observational data link low 25-hydroxyvitamin D levels to both prevalent blood pressure and incident hypertension. No clinical trial has yet examined the effect of vitamin D supplementation in isolated systolic hypertension, the most common pattern of hypertension in older people.. To test whether high-dose, intermittent cholecalciferol supplementation lowers blood pressure in older patients with isolated systolic hypertension.. Parallel group, double-blind, placebo-controlled randomized trial.. Primary care clinics and hospital clinics.. Patients 70 years and older with isolated systolic hypertension (supine systolic blood pressure >140 mm Hg and supine diastolic blood pressure <90 mm Hg) and baseline 25-hydroxyvitamin D levels less than 30 ng/mL were randomized into the trial from June 1, 2009, through May 31, 2011.. A total of 100,000 U of oral cholecalciferol or matching placebo every 3 months for 1 year.. Difference in office blood pressure, 24-hour blood pressure, arterial stiffness, endothelial function, cholesterol level, insulin resistance, and b-type natriuretic peptide level during 12 months.. A total of 159 participants were randomized (mean age, 77 years). Mean baseline office systolic blood pressure was 163/78 mm Hg. Mean baseline 25-hydroxyvitamin D level was 18 ng/mL. 25-Hydroxyvitamin D levels increased in the treatment group compared with the placebo group (+8 ng/mL at 1 year, P < .001). No significant treatment effect was seen for mean (95% CI) office blood pressure (−1 [−6 to 4]/−2 [−4 to 1] mm Hg at 3 months and 1 [−2 to 4]/0 [−2 to 2] mm Hg overall treatment effect). No significant treatment effect was evident for any of the secondary outcomes (24-hour blood pressure, arterial stiffness, endothelial function, cholesterol level, glucose level, and walking distance). There was no excess of adverse events in the treatment group, and the total number of falls was nonsignificantly lower in the group receiving vitamin D (36 vs 46, P = .24).. Vitamin D supplementation did not improve blood pressure or markers of vascular health in older patients with isolated systolic hypertension.. isrctn.org Identifier: ISRCTN92186858.

Topics: Aged; Blood Pressure; Cholecalciferol; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Follow-Up Studies; Humans; Hypertension; Prospective Studies; Systole; Treatment Outcome; Vitamins

Vitamin D deficiency and obesity are associated with increased tissue renin-angiotensin system (RAS) activity.. The objective of the study was to evaluate whether vitamin D(3) therapy in obesity reduces tissue-RAS activity, as indicated by an increase in tissue sensitivity to angiotensin II (AngII).. Participants included obese subjects with hypertension and 25-hydroxyvitamin D less than 25 ng/ml.. Subjects were studied before and after 1 month of vitamin D(3) 15,000 IU/d, while in dietary sodium balance, and off all interfering medications. Fourteen subjects successfully completed all study procedures.. The study was conducted at a clinical research center.. At each study visit, tissue sensitivity to AngII was assessed by measuring renal plasma flow (RPF), mean arterial pressure (MAP), and adrenal secretion of aldosterone during an infusion of AngII. Subjects were then given captopril, and a second AngII infusion to evaluate the effect of captopril on tissue-RAS activity.. Vitamin D(3) therapy increased 25-hydroxyvitamin D (18 to 52 ng/ml) and basal RPF (+5%) and lowered supine MAP (-3%) (all P < 0.01). There was a greater decline in RPF and higher stimulation of aldosterone with AngII infusion after vitamin D(3) therapy (both P < 0.05). As anticipated, captopril increased the renal-vascular, MAP, and adrenal sensitivity to AngII, but this effect was much smaller after vitamin D(3) therapy, indicating that vitamin D(3) therapy corrected the tissue sensitivity to AngII akin to captopril.. Vitamin D(3) therapy in obese hypertensives modified RPF, MAP, and tissue sensitivity to AngII similar to converting enzyme inhibition. Whether chronic vitamin D(3) therapy abrogates the development of diseases associated with excess RAS activity warrants investigation.

Topics: Adult; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Captopril; Cholecalciferol; Drug Resistance; Drug Synergism; Female; Humans; Hypertension; Male; Middle Aged; Obesity; Renal Plasma Flow; Vitamin D Deficiency

To assess effects of vitamin D and Calcium (Ca) on hormonal and metabolic milieu of polycystic ovary syndrome (PCOS).. Single arm open label trial.. Twelve overweight and vitamin D deficient women with PCOS underwent a 2 hour oral glucose tolerance testing at baseline and following 3-month supplementation with vitamin D (daily dose of 3533 IU, increased to 8533 IU after the first five participants) and 530 mg elemental Ca daily.. Blood pressure (BP), plasma glucose, insulin, total testosterone (T) androstenedione (A), sex hormone binding globulin, lifestyle parameters were assessed at baseline and following 3-month intervention. Insulin resistance (IR) and area under the curve for glucose and insulin were computed; paired analyses were conducted.. Improved serum 25OHD (p < 0.001) and reductions in total T (p = 0.036) and A (p = 0.090) levels were noted following 3-month supplementation, compared to baseline. Significant lowering in BP parameters was seen in participants with baseline BP ≥ 120/80 mmHg (n = 8) and in those with baseline serum 25OHD ≤20 ng/ml (n = 9). Parameters of glucose homeostasis and IR remained unchanged (p > 0.05).. Androgen and BP profiles improved followed three month intervention, suggesting therapeutic implications of vitamin D and Ca in overweight and vitamin D deficient women with PCOS.

Topics: 25-Hydroxyvitamin D 2; Adult; Body Mass Index; Calcifediol; Calcium, Dietary; Cholecalciferol; Cohort Studies; Dietary Supplements; Ergocalciferols; Female; Humans; Hyperandrogenism; Hypertension; Overweight; Patient Dropouts; Pilot Projects; Polycystic Ovary Syndrome; Testosterone Congeners; Vitamin D Deficiency; Young Adult

Low 25-hydroxy-vitamin D (25(OH)D) levels are inversely related to blood pressure (BP) and have been associated with incident hypertension. In people living at northern latitudes diminished cholecalciferol synthesis in the winter increases the risk of vitamin D deficiency. We wanted to test the hypothesis that daily cholecalciferol supplementation in the winter lowers BP in patients with hypertension.. We investigated the effect of 75 µg (3,000 IU) cholecalciferol per day in a randomized, placebo-controlled, double-blind study in 130 hypertensive patients residing in Denmark (56º N). Ambulatory BP (24-h BP) and arterial stiffness were measured before and after 20 weeks of treatment, that took place between October and March.. A total of 112 patients (mean age 61 ± 10) with a baseline p-25(OH)D of 23 ± 10 ng/ml completed the study. Compared with placebo, a nonsignificant 3/1 mm Hg (P = 0.26/0.18) reduction was found in 24-h BP. In patients with vitamin D insufficiency (<32 ng/ml) at baseline (n = 92), 24-h BP decreased by 4/3 mm Hg (P = 0.05/0.01). Central BP (CBP) estimated by applanation tonometry and calibrated with a standardized office BP was reduced by 7/2 mm Hg (P = 0.007/0.15) vs. placebo. No differences in carotid-femoral pulse wave velocity (PWV) or central augmentation index (AIx) were found between treatment arms.. Cholecalciferol supplementation, by a dose that effectively increased vitamin D levels, did not reduce 24-h BP, although central systolic BP decreased significantly. In a post-hoc subgroup analysis of 92 subjects with baseline p-25(OH)D levels <32 ng/ml, significant decreases in 24-h systolic and diastolic BP occurred during cholecalciferol supplementation.

Topics: Aged; Blood Pressure; Cholecalciferol; Denmark; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Seasons; Vascular Stiffness; Vitamin D Deficiency

We aimed to determine the effect of a monthly oral vitamin D on the serum 25-hydroxyvitamin D levels and iPTH levels in patients with CKD.. This was a prospective controlled trial of 48 patients with CKD stage 3-4. Patients were divided into two groups Group1 the cholecalciferol treatment group, Group 2, the control group. One patient in Group 1, and 3 patients in Group2 were excluded after the baseline 25(OH)D levels were determined to be greater than 30ng/ml. Two patients in Group1, and one patient in Group 2 were excluded after the baseline iPTH was determined to be less than 70 pg/ml and greater than 300 pg/ml. Five patients in both groups were lost to follow-up. Thus, a total of 16 patients in Group 1 and 15 patients in Group2 completed the three month study. Group1 patients received 300,000 IU month oral cholecalciferol.. The mean serum 25(OH)D concentration of the group1 was significantly higher at baseline (P=0.039). At the end of the three months; serum 25 (OH) D level increased significantly in Group1 (P=0.001). iPTH level of Group1 was significantly lower at baseline (P=0.034). The values of the group1 before and end of third month was compared, serum Ca (P=0.011), P (P=0.013) level showed significant increase, but no significant increase in the Group 2 (P>0.05). The groups had not a clinically significant change in serum Ca and P level (P>0.05).. Oral cholecalciferol supplementation can be used safely and effective in reducing iPTH levels and correcting vitamin D insufficiency/deficiency in patients with CKD.

Topics: Administration, Oral; Adult; Aged; Bone Density Conservation Agents; Cholecalciferol; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Follow-Up Studies; Glomerulonephritis; Humans; Hyperparathyroidism; Hypertension; Male; Middle Aged; Parathyroid Hormone; Prospective Studies; Renal Insufficiency, Chronic; Risk Factors; Treatment Outcome; Vitamin D

Vitamin D has been reported to lower blood pressure in vivo by regulating the renin-angiotensin system; however, there are limited clinical studies to support this finding in humans. We investigated the effect of vitamin D treatment on hypertension in a three-arm randomized placebo controlled pilot and feasibility study. We tested placebo with two forms of vitamin D: cholecalciferol (vitamin D(3)) and the active form of vitamin D, calcitriol. Subjects were recruited from the Atlanta Veterans Affairs Medical Center in Decatur, GA between April and August 2008. Subjects received 200,000IU of vitamin D(3) (n=3) weekly for 3 weeks or matching placebo (n=3) weekly for 3 weeks (n=3) or 0.5mug calcitriol (n=2) taken twice daily for one week. Our primary endpoint was blood pressure measured by 24h ambulatory blood pressure monitor. Subjects receiving calcitriol experienced a 9% decrease in mean systolic blood pressure (SBP) compared placebo (p<0.001). One week after conclusion of calcitriol therapy SBP returned to pre-treatment levels. There was no reduction in blood pressure in the placebo or vitamin D(3) groups. Results from this pilot study suggests that active vitamin D therapy may be an effective short-term intervention for reducing blood pressure and needs to be explored further in larger controlled studies.

Topics: Adult; Biomarkers; Black or African American; Blood Pressure; Calcitriol; Cholecalciferol; Feasibility Studies; Humans; Hypertension; Middle Aged; Pilot Projects; Placebos; Renin; Systole

In arterial hypertension, increased Th17 cells and reduced Tregs are the hallmarks of immunological dysfunction and the basis for the investigation of immunomodulatory drugs. Although cholecalciferol is not a primary immunomodulator, it has recognized action on immune cells, leading us to hypothesise if cholecalciferol can induce a more tolerogenic phenotype in obese hypertensives. In a phase-2, single-centre, randomised, open, 24-week trial, we assigned adults with obesity-associated hypertension and vitamin D deficiency to receive usual therapy plus 50,000 IU/week of cholecalciferol or usual therapy alone. The primary endpoint was the percentual variation in T CD4

Topics: Adipose Tissue; Cholecalciferol; Humans; Hypertension; Obesity; T-Lymphocytes, Regulatory; Th17 Cells

The aim of work was to evaluate the efficacy of combination therapy with vitamin D metabolites on mineral bone density and markers of bone remodeling in postmenopausal women with arterial hypertension, obesity and vitamin D deficiency working in adverse environmental conditions. We examined 95 women aged from 48 to 60 years, 79 people (main group) had arterial hypertension, obesity and deficiency vitamin D and worked in adverse conditions of production, 16 were healthy women. The main group depending on the conducted treatment were divided into 3 groups: А group - received standard antihypertensive therapy, Cholecalciferol and Alfacalcidol; group B - standard antihypertensive therapy and Cholecalciferol; group C - standard antihypertensive therapy. The examination included anthropometric measurements (body weight, height, calculation of body mass index, waist circumference, hip circumference, calculation of index waist circumference / hip circumference), measurement of blood pressure, laboratory tests - determination of the 25-hydroxyvitamin D, parathyroid hormone, C-terminal telopeptide, osteocalcin, osteoprotegerin, instrumental study of mineral density of bone tissue (the definition of T-criterion). The dynamics of the level of 25-hydroxyvitamin D, parathyroid hormone, C-terminal telopeptide, osteocalcin, osteoprotegerin and mineral density of bone tissue after 6 and 12 months. The results showed a positive effect of Cholecalciferol and Alfacalcidol on the level of 25-hydroxyvitamin D, markers of bone formation in serum and parameters of mineral bone density in women. However, combination therapy with vitamin D metabolites showed a more pronounced effect on the processes of bone formation and mineral density of bone tissue (p<0.05). Found that the lack of correction of deficiency and insufficiency of vitamin D contributes to the progressive decrease in mineral density of bone tissue and disruption of the processes of bone formation. Combination therapy with vitamin D metabolites is effective (p<0.05) and pathogenetically justified in the treatment of vitamin D deficiency and structural and functional changes of bone tissue in postmenopausal women with arterial hypertension and obesity, working in adverse environmental conditions.

Topics: Bone and Bones; Bone Density; Cholecalciferol; Female; Humans; Hypertension; Middle Aged; Obesity; Parathyroid Hormone; Vitamin D; Vitamin D Deficiency

Accumulating studies have suggested that gut microbiota (GM) dysbiosis and vitamin D3 deficiency each play an important role during the progression of hypertension (HTN). However, few studies have characterized the underlying interaction between GM shift and vitamin D3 deficiency in HTN patients.. This study aimed to evaluate the possible crosstalk between GM dysbiosis and vitamin D deficiency in the pathogenesis of HTN.. In a cohort of 34 HTN patients and 15 healthy controls, we analyzed the fecal microbiota products, GM composition, and the interaction between GM and vitamin D3.. Vitamin D3 was significantly decreased in feces of HTN patients (P = .006, vs controls) and was correlated with altered GM, including decreased Shannon index (R. Our findings suggest that the GM dysbiosis contributing to the development of HTN might be partially mediated by vitamin D3 deficiency. Future studies involving the underlying mechanism and intervention strategies targeting microbiome composition and vitamin D3 to counteract the progression of HTN are warranted.

Topics: Blood Pressure; Cholecalciferol; Chromatography, Liquid; Disease Progression; Dysbiosis; Feces; Female; Gastrointestinal Microbiome; Humans; Hypertension; Male; Middle Aged; Vitamin D Deficiency

To evaluate the effect of 25 (OH) vitamin D supplementation on blood pressure (BP) variability in hypertensive women in the pre-menopausal and post-menopausal periods.. 881 hypertensive women prospectively followed for an interventional study between January 2016 and September 2017, in specialized consultation at the department of internal medicine at the Blida University Hospital (Algeria). Four hundred and thiry nine premenopausal women (group I) and 442 menopausal women (group II). The initial serum 25 (OH) D level for each group was determined by the enzyme immunoassay. In groups I and II, we identified 2 subgroups, A: insufficiency (vit D between 29 and 20ng/ml) and B: deficiency (vit D less than 20ng/L). Antihypertensive therapy was supplemented with an additional 200000IU/month cholecalciferol for the two B subgroups. The variability in BP was calculated as the ratio of mean systolic and diastolic BP during daytime and nighttime, with performing ambulatory BP measurement at baseline, 3, 6, and 12 months of follow-up.. At inclusion, the level of 25 (OH) D was lower (P<0.05) in subgroups IB (19.3±8.5ng/ml) and IIB (18.2±9, 5ng/ml) compared to subgroups IA (28.1±10.7ng/ml) and IIA (25.2±10.1ng/ml). After supplementation, the level of 25 (OH) D increased in subgroup IB (38.3±11.9ng/ml) and in subgroup IIB (37.3±10, 5ng/ml) and became higher (P<0.001) than in subgroups IA and IIA. Between subgroups IA and IB, at inclusion, there is no difference (P>0.05) in the SBP and DBP variability during the day and at night. After treatment, the variability of the SBP at night became lower (P<0.02) in group IB compared to group IA. In subgroup IIB, daytime variability indices were higher (P=0.04) at inclusion than in group IIA. After treatment, the variability of SBP during the day decreased but remained the highest (P<0.05) in subgroup IIB (14.8±10.8mmHg) compared to subgroup IB (12.0±8.1mmHg), as well as to subgroups IIA (10.9±9.8mmHg) and IA (10±8.1mmHg). We found a significant correlation of cholecalciferol with the variability of SBP during the day.. Vitamin D deficiency appears to be a factor of BP variability. Although the variability of the postmenopausal group remains higher than that of the other groups, the correction of the level of 25 (OH) D by the supply of cholecalciferol 200000 IU per month leads to a reduction in the variability of BP in the studied hypertensive women could help to prevent morbimortal complications.

Topics: Algeria; Blood Pressure; Cholecalciferol; Female; Humans; Hypertension; Menopause; Middle Aged; Premenopause; Prospective Studies; Vitamin D Deficiency

To evaluate the effect of cholecalciferol and diuretics as components of combination antihypertensive therapy (CAHT) on plasma renin activity (PRA) and endothelial function in patients with arterial hypertension (AH).. We included in this prospective study 153 patients with II-degree AH. Duration of follow-up was 15.8±1.8 months. Patients were divided into four groups: patients of group 0 received CAHT without cholecalciferol or diuretic; of group 1 - CAHT with cholecalciferol (2000 IU daily); of group 2 - CAHT with diuretic; of group 3 - CAHT with diuretic and cholecalciferol 2000 IU daily.. After treatment, the highest level of 25-hydroxy vitamin D (25(OH)D) (48.9 [34.3; 67.9] ng/ml) and its greatest dynamics (Δ) - (27.5 [6.2; 48.8] ng/mL) were observed in group 1. With diuretics blood level of 25(OH)D and its Δ were lower (p.

Topics: Antihypertensive Agents; Cholecalciferol; Diuretics; Drug Therapy, Combination; Endothelium, Vascular; Female; Humans; Hypertension; Male; Middle Aged; Prospective Studies; Renin

Deficiency of vitamin D3, a lipophilic micronutrient, plays a role in the development of some chronic diseases. Vitamin D3 deficiency affects 25-50% of the human population and has been associated with increased risk for development of hypertension. DNA damage induced by reactive oxygen species (ROS) occurs more often in hypertensive than in normotensive individuals, and vitamin D3 status can influence this relationship. The aim of this study was to evaluate whether a diet supplemented with (10,000 IU/kg) or deficient in (0 IU/kg) vitamin D3, compared to a vitamin D3 control diet (1000 IU/kg), would modulate DNA damage and ROS production in spontaneously hypertensive rats (SHR) and normotensive control Wistar-Kyoto (WKY) rats after 12 weeks of treatment. ROS production was assessed by measuring the oxidative burst of neutrophils. DNA damage was evaluated using the comet assay in peripheral blood and the micronucleus test in bone marrow and peripheral blood. Vitamin D3 supplementation did not induce DNA damage and did not change neutrophil ROS production in SHR and WKY rats. Vitamin D3 deficiency induced neutrophil ROS production and a high frequency of micronucleus formation in the bone marrow and peripheral blood of SHR rats only, and induced DNA damage (comet) in peripheral blood of both SHR and WKY rats. In conclusion, vitamin D3 deficiency showed a more pronounced effect on hypertensive animals. Population studies are needed to test whether this relationship also exists in humans.

Topics: Animals; Cholecalciferol; Dietary Supplements; Disease Models, Animal; DNA Damage; Hypertension; Male; Neutrophils; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reactive Oxygen Species; Respiratory Burst

Vitamin D deficiency is related to an increased prevalence of cardiovascular disease. Renin-angiotensin-aldosterone system suppression and vascular dysfunction are considered among the main mechanisms implicated in this association. However, interventional studies demonstrating that vitamin D replacement reduces circulating renin-angiotensin-aldosterone components and improves vascular function in humans are still lacking.. Thirty-three consecutive patients with essential hypertension and hypovitaminosis D underwent therapy with cholecalciferol 50 000 IU/week orally for 8 weeks. Thirty-three hypertensive patients with normal vitamin D levels and 20 normotensive individuals were also enrolled as control groups. At baseline and at the end of the study, we evaluated plasma renin activity, circulating renin, angiotensin II, aldosterone and plasma vitamin D levels. Endothelial function [flow-mediated dilation (FMD)], carotid-femoral pulse wave velocity and augmentation index, peripheral and central blood pressure were also acquired.. After 8-week cholecalciferol administration, all treated patients normalized plasma 25(OH)D values. Furthermore, a reduction in plasma levels of plasma renin activity (1.17 ± 0.3 vs 1.51 ± 0.4 ng/ml per h, P = 0.02), renin (13.4 ± 1.7 vs 19.2 ± 2.9 pg/ml, P < 0.001), angiotensin II (11.6 ± 1.6 vs 15.8 ± 2.7 pg/ml, P = 0.02) was observed at the end of the study. FMD was significantly increased after cholecalciferol treatment (4.4 ± 2.6 vs 3.3 ± 2.1%, P < 0.05), in the absence of changes of brachial artery diameter and endothelium-independent vasodilation. Carotid-femoral pulse wave velocity and augmentation index were not modified, as well peripheral and central blood pressure.. The restoration of normal vitamin D levels after 8-week cholecalciferol treatment is able to inhibit peripheral renin-angiotensin system and improve FMD in essential hypertensive patients with hypovitaminosis D.

Topics: Adult; Aldosterone; Angiotensin II; Blood Pressure; Cardiovascular Diseases; Cholecalciferol; Endothelium; Essential Hypertension; Female; Humans; Hypertension; Male; Middle Aged; Pulse Wave Analysis; Renin; Renin-Angiotensin System; Vasodilation; Vitamin D; Vitamin D Deficiency; Vitamins

The lower threshold plasma 25-hydroxy vitamin D (25(OH)D) level for optimal cardiovascular health is unclear, whereas the toxicity threshold is less clear. The aim of this study was to examine the cardiovascular-vitamin D dose-response curve in a normal rat model. Doses of cholecalciferol ranged from deficiency to toxic levels (equivalent to human doses of 0, 0·015, 0·25 and 3·75mg/d) for 4 weeks, and then cardiovascular health was examined using blood pressure telemetry and high-resolution ultrasound in normal male rats (n 16/group, 64 rats total). After 1 month, only the 0·25mg/d group had plasma 25(OH)D that was within current recommended range (100-125 nmol/l), and all groups failed to change plasma Ca or phosphate. Systolic blood pressure increased significantly (10-15 mmHg) in the rat groups with plasma 25(OH)D levels at both 30 and 561 nmol/l (groups fed 0 and 3·75mg/d) compared with the group fed the equivalent to 0·015mg/d (43 nmol/l 25(OH)D). Although not significant, the group fed the equivalent to 0·25mg/d (108 nmol/l 25(OH)D) also showed a 10 mmHg increase in systolic blood pressure. Carotid artery diameter was significantly smaller and wall thickness was larger, leading to higher peak carotid systolic blood velocity in these two groups. Despite these vascular changes, cardiac function did not differ among treatment groups. The key finding in this study is that arterial stiffness and systolic blood pressure both showed a U-shaped dose-response for vitamin D, with lowest values (best cardiovascular health) observed when plasma 25(OH)D levels were 43 nmol/l in normal male rats.

Topics: Animals; Blood Pressure; Calcifediol; Calcium; Cardiac Output; Carotid Arteries; Cholecalciferol; Diet, Vegetarian; Disease Models, Animal; Echocardiography; Heart; Hypertension; Male; Phosphates; Rats, Wistar; Stroke Volume; Time Factors; Ultrasonography, Doppler; Vascular Stiffness; Vitamin D Deficiency

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

This study investigated the effects of hypertension on regional aortic biomechanical and structural properties in three rat models of vascular calcification: the hypertensive Lewis polycystic kidney (LPK; n = 13) model of chronic kidney disease, spontaneously hypertensive rats (SHRs; n = 12), and calcification in normotensive Lewis rats induced by vitamin D3 and nicotine (VDN; n = 8). Lewis and Wistar-Kyoto rats were controls. Thoracic and abdominal aortic stiffness parameters were assessed by tensile testing. In models where aortic stiffness differences compared with controls existed in both thoracic and abdominal segments, an additional cohort was quantified by histology for thoracic and abdominal aortic elastin, collagen, and calcification. LPK and VDN animals had higher thoracic breaking strain than control animals (P < 0.01 and P < 0.05, respectively) and lower energy absorption within the tensile curve of the abdominal aorta (P < 0.05). SHRs had a lower abdominal breaking stress than Wistar-Kyoto rats. LPK and VDN rats had more elastic lamellae fractures than control rats (P < 0.001), which were associated with calcium deposition (thoracic R = 0.37, P = 0.048; abdominal: R = 0.40, P = 0.046). LPK rats had higher nuclear density than control rats (P < 0.01), which was also evident in the thoracic but not abdominal aorta of VDN rats (P < 0.01). In LPK and VDN rats, but not in control rats, media thickness and cross-sectional area were at least 1.5-fold greater in thoracic than abdominal regions. The calcification models chronic kidney disease and induced calcification in normotension caused differences in regional aortic stiffness not seen in a genetic form of hypertension. Detrimental abdominal aortic remodeling but lower stiffness in the thoracic aorta with disease indicates possible compensatory mechanisms in the proximal aorta.

Topics: Animals; Aorta, Abdominal; Aorta, Thoracic; Biomechanical Phenomena; Cholecalciferol; Collagen; Disease Models, Animal; Elastin; Female; Hemodynamics; Hypertension; Male; Oxazines; Rats; Rats, Inbred Lew; Rats, Inbred SHR; Rats, Inbred WKY; Renal Insufficiency, Chronic; Tensile Strength; Vascular Calcification; Vascular Stiffness

Vitamin D deficiency is one of the most common chronic medical conditions in the world and also prevalent in Australia. A growing body of evidence suggests that low vitamin D also has adverse effects on cardiovascular health, including coronary risk factors and adverse cardiovascular outcomes such as myocardial infarction, cardiac failure and stroke. There is some evidence suggesting that a greater proportion of people with cardiovascular disease have low vitamin D compared to the general population. We examined the prevalence of vitamin D deficiency and insufficiency in elective cardiothoracic surgical patients presenting to the Alfred Hospital in Melbourne, Australia and compared this to recent Victorian statistics for people of the same age group.. Consecutive adult elective cardiothoracic surgical patients listed for either coronary artery bypass graft surgery or heart valve repair or replacement surgery attending The Alfred Hospital, Melbourne between July 2011 and October 2012 were invited to participate. This ensured that patients were enrolled over all four seasons. Fasting serum samples were taken on the day of surgery, immediately after admission. Eighty volunteers participated in the study. Of the group, 40% were due to have coronary artery bypass graft surgery, 35% valve surgery and 25% a combination of the two; 74% reported having hypertension, 69% hyperlipidaemia, 26% diabetes and 39% had a BMI >30 kg/m(2).. Test results revealed that 92.5% of patients had Vitamin D levels < 75 nmol/L, 67.5% had levels < 60 nmol/L, 52.5% had levels between 30-59 nmol/L and 15% had levels < 30 nmol/L. Inadequate vitamin D levels were found in 80% of obese patients (BMI > 30 kg/m(2)) compared to 59% of non-obese patients.. Based on our small screening study, a substantial proportion of elective cardiothoracic surgical patients have less than optimal serum vitamin D3 levels prior to surgery. We found two-thirds of patients had serum vitamin D levels below 60 nmol/L, placing them at higher risk of falls. This finding is of concern as these patients would have received multiple consultations with various medical practitioners prior to hospital admission and yet their inadequate vitamin D status remained. Failing to identify patients with low vitamin D and correcting it with supplementation places older adults at unnecessary risk, especially of falls, which are associated with a high risk of mortality. In an ageing population with CVD, vitamin D status needs to be assessed and any inadequacy corrected. Whether low vitamin D status prior to cardiac surgery affects post-surgery outcomes, is another issue which deserves future investigation.

Topics: Aged; Australia; Cardiac Surgical Procedures; Cardiac Valve Annuloplasty; Cholecalciferol; Coronary Artery Bypass; Diabetes Mellitus; Female; Heart Valve Prosthesis Implantation; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Obesity; Prevalence; Vitamin D Deficiency

Vitamin D plasma levels are negatively associated with blood pressure and cardiovascular mortality, and vitamin D supplementation reduces cardiovascular events. Renin-angiotensin system (RAS) suppression may be one of the mechanisms involved. However, there are no interventional prospective studies demonstrating a reduction in circulating RAS components after vitamin D treatment.. Fifteen consecutive drug-free patients with essential hypertension and hypovitaminosis D underwent therapy with an oral dose of 25000 I.U. of cholecalciferol once a week for two months, while maintaining a constant-salt diet. In basal conditions and at the end of the study, RAS activity (plasma angiotensinogen, renin, PRA, angiotensin II, aldosterone and urinary angiotensinogen) was investigated, in addition to blood pressure and plasma vitamin D levels (25(OH)D).. After cholecalciferol administration, all patients exhibited normalized plasma 25(OH)D values. At the end of the study, a reduction (p < 0.05) in plasma renin and aldosterone, and a decrement, although not significant, of PRA and angiotensin II, was observed. No difference was found in plasma and urinary angiotensinogen or blood pressure values.. Our data indicate that in essential hypertensives with hypovitaminosis D, pharmacological correction of vitamin D levels can blunt systemic RAS activity.

Topics: Adult; Aged; Aldosterone; Angiotensin II; Cholecalciferol; Essential Hypertension; Female; Humans; Hypertension; Male; Middle Aged; Renin; Renin-Angiotensin System; Vitamin D; Vitamin D Deficiency

Topics: Blood Pressure; Cholecalciferol; Humans; Hypertension

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of kidney failure in the world. Currently there are no treatments to prevent kidney due to ADPKD. Vitamin D is traditionally known for its role in maintaining calcium balance and normal bone health, but it is being increasingly being recognised for a number of other important physiological functions, including reducing blood pressure and proteinuria as well as kidney inflammation andfibrosis. Vitamin D deficiency is associated with proteinuria, increased mortality and may mediate the progression to kidney failure. Recent data from an Australian cohort study (AusDiab) reveals that vitamin D deficiency and insufficiency are common conditions, affecting 26.6% and 42.1% of the Australian community respectively. Preclinical studies from our laboratory have identified that vitamin D deficiency exacerbates proteinuria and hypertension in experimental PKD, and that this is reversed by treatment with vitamin D receptor agonist. In this manuscript, we report the rational and design of an open-label observational study of humans with ADPKD (eGFR>30 ml/min/1.73m2). All subjects will undergo screening for vitamin D levels at the beginning of study, and those that are found to be either deficient (<50 nmol/L) or insufficient (<75 nmol/L) will be repleted with oral cholecalciferol for 6 months. We predict that cholecalciferol will attenuate hypertension, proteinuria and reduce the urinary excretion of a biomarker, monocyte chemoattractant protein-1 (MCP-1, a surrogate inflammatory marker of progression in ADPKD). This study will provide evidence as to whether a simple intervention such as vitamin D repletion, in either deficient or insufficient states, is a treatment to prevent kidney failure in ADPKD.

Topics: Adolescent; Adult; Aged; Australia; Biomarkers; Chemokine CCL2; Cholecalciferol; Disease Progression; Female; Humans; Hypertension; Male; Middle Aged; Polycystic Kidney, Autosomal Dominant; Proteinuria; Research Design; Vitamin D; Vitamin D Deficiency; Young Adult

Topics: Biomarkers; Blood Pressure; Cholecalciferol; Dietary Supplements; Humans; Hypertension; Systole; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Topics: Blood Pressure; Cholecalciferol; Female; Humans; Hypertension; Male; Vitamin D Deficiency

Aldosterone (Aldo) is an important active hormone in the renin-angiotensin-aldosterone system and plays a vital role in the development of hypertension, heart failure and other cardiovascular diseases. We aimed to explore the role of endogenous Aldo in aortic calcification in rats. We induced arterial calcification in rats by intramuscular administration of vitamin D(3) plus oral nicotine (VDN) and determined calcium content, (45)Ca(2+) accumulation and activity of alkaline phosphatase (ALP). The mRNA level of osteopontin (OPN) was measured by semi-quantitative reverse transcriptase polymerase chain reaction. Deposition of collagen in the aorta wall was measured by Sirius red staining. The content of angiotensin II (Ang II) and Aldo in plasma and myocardial and vascular tissue was determined by radioimmunoassay. In rats with VDN treatment, von Kossa staining showed calcification in vascular smooth muscle cells and extracellular matrix, and the content of calcium in calcified arteries was 5.8-fold of that in control arteries (P < 0.01). The accumulation of (45)Ca(2+) and activity of ALP in calcified aortic tissue was three- and 2.5-fold, respectively, that in control tissue (P < 0.01). The mRNA expression of OPN was significantly higher, by 58%, in calcified than control tissue (P < 0.01). Vascular fibrosis was greater in rats with calcified tissue than in control rats. The level of Ang II and Aldo was 58% and 80% higher, respectively, in calcified than control tissue (both P < 0.01). The changes could be significantly improved by treatment with captopril, an angiotensin-converting enzyme inhibitor, and the Aldo receptor antagonist spironolactone. These results suggest that Aldo is an endogenous bioactive factor involved in vascular calcification.

Topics: Aldosterone; Alkaline Phosphatase; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta; Calcium; Captopril; Cholecalciferol; Collagen; Fibrosis; Hypertension; Male; Mineralocorticoid Receptor Antagonists; Nicotine; Osteopontin; Rats; Rats, Sprague-Dawley; RNA, Messenger; Spironolactone; Vascular Calcification

The Dahl salt-sensitive rat, a model for salt-induced hypertension, develops hypovitaminosis D during high salt intake, which is caused by loss of protein-bound vitamin D metabolites into urine. We tested the hypothesis that high dietary cholecalciferol (5- and 10-fold standard) would increase plasma 25-hydroxycholecalciferol (25-OHD(3)) concentration (indicator of vitamin D status) of salt-sensitive rats during high salt intake. Salt-sensitive rats were fed 0.3% salt (low salt, LS), 3% salt (HS), 3% salt and 7.5 microg cholecalciferol/d (HS-D5), or 3% salt and 15 microg cholecalciferol/d (HS-D10) and sacrificed at week 4. Plasma 25-OHD(3) concentrations of the two groups of HS-D rats were similar to that of LS rats and more than twice that of HS rats. Urinary cholecalciferol metabolite content of HS-D rats was more than seven times that of HS rats. Systolic blood pressures of the hypertensive HS and HS-D rats did not significantly differ, whereas LS rats were not hypertensive. We conclude that high dietary cholecalciferol increases plasma 25-OHD(3) concentration, but does not attenuate the hypertension of salt-sensitive rats during high salt intake. Low salt intake may be necessary to both maintain optimal vitamin D status and prevent hypertension in salt-sensitive individuals.

Topics: Animals; Calcifediol; Cholecalciferol; Diet; Dose-Response Relationship, Drug; Female; Hypertension; Parathyroid Hormone; Rats; Rats, Inbred Dahl; Sodium Chloride, Dietary; Time Factors

Topics: Animals; Calcifediol; Cholecalciferol; Female; Genotype; Humans; Hypertension; Male; Mice; Polymorphism, Genetic; Receptors, Calcitriol; Renin; Risk Factors; Vitamin D; Vitamin D Deficiency

Topics: Aldosterone; Animals; Blood Pressure; Cholecalciferol; Disease Models, Animal; Hypertension; Potassium; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sodium

The vitamin D(3) and nicotine (VDN) model is a model of isolated systolic hypertension (ISH) due to arterial calcification raising arterial stiffness and vascular impedance similar to an aged and stiffened arterial tree. We therefore analyzed the impact of this aging model on normal and diseased hearts with myocardial infarction (MI). Wistar rats were treated with VDN (n = 9), subjected to MI by coronary ligation (n = 10), or subjected to a combination of both MI and VDN treatment (VDN/MI, n = 14). A sham-treated group served as control (Ctrl, n = 10). Transthoracic echocardiography was performed every 2 wk, whereas invasive indexes were obtained at week 8 before death. Calcium, collagen, and protein contents were measured in the heart and the aorta. Systolic blood pressure, pulse pressure, thoracic aortic calcium, and end-systolic elastance as an index of myocardial contractility were highest in the aging model group compared with MI and Ctrl groups (P(VDN) < 0.05, 2-way ANOVA). Left ventricular wall stress and brain natriuretic peptide (P(VDNxMI) = not significant) were highest, while ejection fraction, stroke volume, and cardiac output were lowest in the combined group versus all other groups (P(VDNxMI) < 0.05). The combination of ISH due to this aging model and MI demonstrates significant alterations in cardiac function. This model mimics several clinical phenomena of cardiovascular aging and may thus serve to further study novel therapies.

Topics: Aging; Animals; Cardiomyopathies; Cardiovascular System; Cholecalciferol; Disease Models, Animal; Hypertension; Male; Myocardial Contraction; Myocardial Infarction; Nicotine; Rats; Rats, Wistar; Stroke Volume; Ventricular Dysfunction, Left

The vitamin D(3) and nicotine (VDN) model is one of isolated systolic hypertension (ISH) in which arterial calcification raises arterial stiffness and vascular impedance. The effects of VDN treatment on arterial and cardiac hemodynamics have been investigated; however, a complete analysis of ventricular-arterial interaction is lacking. Wistar rats were treated with VDN (VDN group, n = 9), and a control group (n = 10) was included without the VDN. At week 8, invasive indexes of cardiac function were obtained using a conductance catheter. Simultaneously, aortic pressure and flow were measured to derive vascular impedance and characterize ventricular-vascular interaction. VDN caused significant increases in systolic (138 +/- 6 vs. 116 +/- 13 mmHg, P < 0.01) and pulse (42 +/- 10 vs. 26 +/- 4 mmHg, P < 0.01) pressures with respect to control. Total arterial compliance decreased (0.12 +/- 0.08 vs. 0.21 +/- 0.04 ml/mmHg in control, P < 0.05), and pulse wave velocity increased significantly (8.8 +/- 2.5 vs. 5.1 +/- 2.0 m/s in control, P < 0.05). The arterial elastance and end-systolic elastance rose significantly in the VDN group (P < 0.05). Wave reflection was augmented in the VDN group, as reflected by the increase in the wave reflection coefficient (0.63 +/- 0.06 vs. 0.52 +/- 0.05 in control, P < 0.05) and the amplitude of the reflected pressure wave (13.3 +/- 3.1 vs. 8.4 +/- 1.0 mmHg in control, P < 0.05). We studied ventricular-arterial coupling in a VDN-induced rat model of reduced arterial compliance. The VDN treatment led to development of ISH and provoked alterations in cardiac function, arterial impedance, arterial function, and ventricular-arterial interaction, which in many aspects are similar to effects of an aged and stiffened arterial tree.

Topics: Animals; Cardiac Volume; Cholecalciferol; Compliance; Coronary Vessels; Dose-Response Relationship, Drug; Elasticity; Ganglionic Stimulants; Heart Ventricles; Hemodynamics; Hypertension; Male; Models, Cardiovascular; Nicotine; Rats; Rats, Wistar; Vascular Resistance; Ventricular Function

The present study was designed to test the hypothesis that arterial baroreflex dysfunction promotes the development of atherosclerosis. Experiment 1: the baroreflex sensitivity (BRS) was measured in 30 Sprague-Dawley (SD) rats in conscious state with a computerized blood pressure monitoring system. Four weeks later, the rats were administered with Vitamin D3, and fed with the high-cholesterol diet for 8 weeks to induce atherosclerosis. The hearts and aortae were removed for pathological examination. A negative correlation was found between BRS and the scores of coronary (r=-0.464, P<0.01) or aortic atherosclerosis (r=-0.524, P<0.01) in SD rats. Experiment 2: sinoaortic denervation (SAD) was performed in SD rats. Then atherosclerosis was also induced. The atherosclerosis scores in SAD rats were significantly higher than those in sham-operated rats (aortic score: 1.50+/-0.41 versus 1.10+/-0.39, P<0.05; coronary score: 1.70+/-0.35 versus 1.25+/-0.54, P<0.05). Using immunohistochemistry and Western blotting methods, it was found that the expressions of C-reactive protein, intercellular adhesion molecule-1 and vascular-cell adhesion molecule-1 in coronary artery and aorta were increased in SAD rats compared with sham-operated rats. These results indicate that arterial baroreflex dysfunction promotes the development of atherosclerosis in rats, and that inflammation may be involved in this process.

Topics: Animals; Aorta; Aortic Diseases; Atherosclerosis; Autonomic Denervation; Baroreflex; C-Reactive Protein; Carotid Arteries; Cholecalciferol; Diet, Atherogenic; Hypercholesterolemia; Hypertension; Intercellular Adhesion Molecule-1; Male; Myocardium; Phenylephrine; Rats; Rats, Sprague-Dawley; Reflex, Abnormal; Vascular Cell Adhesion Molecule-1

Vitamin D deficiency is now recognized as an epidemic in the United States. The major source of vitamin D for both children and adults is from sensible sun exposure. In the absence of sun exposure 1000 IU of cholecalciferol is required daily for both children and adults. Vitamin D deficiency causes poor mineralization of the collagen matrix in young children's bones leading to growth retardation and bone deformities known as rickets. In adults, vitamin D deficiency induces secondary hyperparathyroidism, which causes a loss of matrix and minerals, thus increasing the risk of osteoporosis and fractures. In addition, the poor mineralization of newly laid down bone matrix in adult bone results in the painful bone disease of osteomalacia. Vitamin D deficiency causes muscle weakness, increasing the risk of falling and fractures. Vitamin D deficiency also has other serious consequences on overall health and well-being. There is mounting scientific evidence that implicates vitamin D deficiency with an increased risk of type I diabetes, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and many common deadly cancers. Vigilance of one's vitamin D status by the yearly measurement of 25-hydroxyvitamin D should be part of an annual physical examination.

Topics: Animals; Autoimmune Diseases; Bone and Bones; Cardiovascular Diseases; Cholecalciferol; Diet; Health Status; Humans; Hypertension; Neoplasms; Nutritional Requirements; Sunlight; Vitamin D; Vitamin D Deficiency

We observed 75 subjects with acute vitamin D3 intoxication (AVD3I). The clinical manifestations of this intoxication are kidneys disorders (65.0%), renal insufficiency (51.0%), gastrointestinal tract disorders (23.0%), arterial hypertension (52.0%). After this intoxication these patients are recommended prolonged rehabilitation.

Topics: Adult; Cholecalciferol; Female; Gastrointestinal Diseases; Humans; Hypertension; Male; Middle Aged; Prognosis; Renal Insufficiency; Retrospective Studies

The chronotherapeutic effects of 1-alpha-(OH) vitamin D3, a pro-drug of 1,25(OH)2 vitamin D3 (1,25(OH)2D3), were evaluated by repeated dosing of the drug in aged stroke-prone spontaneously hypertensive male rats, a model of osteoporosis. Animals (7 months old) were kept in rooms with a 12-h light/dark cycle. Drug (0.5 microg/kg) or vehicle was given once daily at 2 or 14 h after lights on for 3 months. The severity of adverse effects such as body weight loss, hypercalcemia and hyperphosphatemia was significantly less when the drug was given at 14 h after lights on (14 HALO). Serum 1,25(OH)2 vitamin D3 concentrations of 2 h after lights on (2 HALO) group and 14 HALO group did not differ significantly after dosing. The decrease in parathyroid hormone (PTH) level 12 weeks after the start of the study was greater in the 14 HALO group than in the 2 HALO group. Urinary excretion of inorganic Ca and P in the 2 HALO group was greater than that in the 14 HALO group. Urinary excretion of deoxypyridiniline, an index of the bone resorption capacity of osteoclasts, was much suppressed in the 14 HALO group, suggesting that the efficacy of vitamin D3 for suppressing bone resorption might vary with the dosing time. The increase in bone density of both femurs, determined by dual-energy X-ray absorption at the end of the study, was greater in the 14 HALO group than in the 2 HALO group. This is the first study to show the dosing time-dependent efficacy and toxicity of active vitamin D3 in an animal model of osteoporosis. These results indicate that a chronopharmacological approach is beneficial for establishing a more effective and/or safer regimen of active vitamin D3 for the treatment of osteoporosis.

Topics: Aging; Amino Acids; Animals; Body Weight; Bone Density; Calcium; Cholecalciferol; Chronotherapy; Disease Models, Animal; Hypercalcemia; Hypertension; Male; Osteoporosis; Parathyroid Hormone; Phosphates; Rats; Rats, Inbred SHR; Steroid Hydroxylases; Time Factors; Weight Loss

In man, i) arteries calcify with age and ii) age-linked arterial calcification is amplified by vascular pathology such as hypertension or arteriosclerosis. Age-linked arterial calcification has a bad prognosis but drugs to prevent it are lacking. This is partially due to the lack of appropriate animal models. This paper looks at the extent to which arteries calcify with age in the rat and whether hypertension or arteriosclerosis amplifies such calcification. Total calcium levels were determined by acid digestion and flame spectrophotometry and intracellular calcium levels ([Ca2+]i) by the intracellular calcium-sensitive dye, fura-2. Arteries contained up to 5 times more calcium than other soft tissues. Arteries progressively calcified with age whereas other soft tissues did not. Accumulation of calcium with age was essentially extracellular. Hypertension had no effect on age-related arterial calcification. Calcification of the same order as in man was produced in a rat model of arteriosclerosis (vitamin D plus nicotine treatment). In conclusion, as in man, age-linked, organ-specific arterial calcification does occur in rats but its intensity is far less. Arterial calcification of a similar degree to that observed in man can be obtained in rats by hypervitaminosis D plus nicotine.

Topics: Aging; Animals; Aorta, Thoracic; Arteriosclerosis; Calcification, Physiologic; Calcium; Cholecalciferol; Hypertension; Male; Nicotine; Rats; Rats, Inbred F344; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Wistar

1. The mechanism responsible for blood pressure reduction in spontaneously hypertensive rats (SHR) after prolonged cholecalciferol treatment was studied. Two-week treatment of SHR with 0.125 mg cholecalciferol kg-1 body weight per day orally caused significant reductions of systolic blood pressure and of the resting perfusion pressure of the mesenteric vascular bed at constant flow. 2. In addition, the treated animals presented a normalization of the maximum vasoconstriction response to noradrenaline and a reduction of the maximum effect of the adrenaline concentration-response curves. This latter effect probably was due to recovery of the impaired Ca(2+)-dependent K+ channels coupled to alpha 2-adrenoceptors since it was prevented by apamin. 3. The treatment with cholecalciferol also normalized the smooth muscle cell membrane potential of de-endothelialized mesenteric arteries of SHR and their hyperpolarizing responses to alpha 2-adrenergic agonists, which were depressed in untreated SHR. 4. In mesenteric rings with endothelium, alpha 2-adrenergic agonists caused similar hyperpolarizing responses in the SHR and in normotensive Wistar (NWR) and Wistar Kyoto (WKY). In non cholecalciferol-treated SHR the hyperpolarizing mediator involved in this effect was NO, while in NWR it was the endothelium-derived hyperpolarizing factor (EDHF). After cholecalciferol treatment, the hyperpolarization induced by alpha 2-adrenergic agonists in SHR smooth muscle cells was mediated by EDHF, as in NWR. 5. Our results indicate that the hypotensive effect of cholecalciferol in the SHR is probably due to the normalization of vascular reactivity, by restoring the functioning of apamin- and ATP-sensitive K+ channels located in the vascular smooth muscle cell membrane, which are impaired in the SHR.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Cholecalciferol; Endothelium, Vascular; Female; Hypertension; Membrane Potentials; Mesenteric Arteries; Potassium Channels; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Wistar

We studied the effect of oral cholecalciferol treatment on the endothelium-dependent vascular relaxation and hyperpolarization induced by acetylcholine (ACh), which is impaired in spontaneously hypertensive rats (SHR). Adult female SHR and normotensive Wistar-Kyoto rat (WKY) controls received 125 microg of cholecalciferol per kilogram body weight per day for 6 weeks. The responses to ACh of the isolated mesenteric vascular bed and mesenteric artery rings were measured, as well as the smooth muscle cell membrane potential. After cholecalciferol treatment, the systolic blood pressure and basal perfusion pressure of the mesenteric vascular bed of the SHR fell to control levels. The relaxant and hyperpolarizing effects of ACh, which are reduced in SHR, were also brought to control levels after cholecalciferol treatment. These effects of ACh were inhibited by N(omega)-nitro-L-arginine in SHR and by apamin in WKY. After cholecalciferol treatment, SHR hyperpolarizing responses showed the same inhibition pattern as those of WKY. This indicates that, after cholecalciferol treatment, SHR vascular mesenteric preparation responses to ACh are mediated by endothelium-derived hyperpolarizing factor, which induces activation of Ca(2+)-dependent K(+) channels, as in WKY. In untreated SHR, the ACh-mediated response is entirely due to ACh acting via the release of nitric oxide.

Topics: Acetylcholine; Animals; Antihypertensive Agents; Blood Pressure; Cholecalciferol; Drug Interactions; Female; Hypertension; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vasodilation; Vasodilator Agents

1. The diet of spontaneously hypertensive rats (SHR) and normotensive Wistar rats (NWR) was supplemented with 12.5 micrograms cholecalciferol per 100 g body weight daily, by gavage, for 4 weeks. 2. The amplitude of the contractile responses of aortic rings from SHR to potassium and adrenaline, which was smaller than in NWR aortae, was increased after treatment with cholecalciferol. No further changes were observed in the responses of NWR and SHR aortae in the presence of 100 nM apamin. 3. The membrane potentials of aortae from SHR, which were higher than those of aortae from NWR, decreased after treatment with cholecalciferol. Further depolarization was observed in aortic rings from NWR, but not in aortic rings from SHR, after their preincubation with 100 nM apamin. 4. It is concluded that cholecalciferol normalizes the membrane potential and contractility of aortae from SHR, probably through an effect on lipid composition and structure of the plasma membrane.

Topics: Animals; Aorta, Thoracic; Apamin; Cell Membrane; Cholecalciferol; Diet; Electrophysiology; Epinephrine; Hypertension; In Vitro Techniques; Membrane Potentials; Muscle Contraction; Muscle, Smooth, Vascular; Potassium Chloride; Rats; Rats, Inbred SHR; Rats, Wistar

We tested whether cardiac mass can be related to decreased aortic stiffness in an original rat model of isolated systolic hypertension. Increased aortic stiffness was produced by calcium overload of elastic arteries after vitamin D3 plus nicotine treatment. Half of the animals were chronically treated with the angiotensin-converting enzyme inhibitor perindopril (1 mg/kg per day PO). Rats were pithed, and lower body vascular resistance was measured. Blood pressure was then increased by phenylephrine infusion, and carotidofemoral pulse wave velocity was measured. This value together with those for thoracic aorta internal diameter and medial thickness (determined after in situ fixation and histomorphometry) were used to calculate elastic modulus. Vitamin D3 plus nicotine treatment produced parallel increases in cardiac mass and elastic modulus, with a significant correlation between the two. There was no significant change in resistance. Treatment with perindopril reversed the changes in cardiac mass and elastic modulus but had no effect on resistance after calcium overload of the elastic arteries. In this model of isolated systolic hypertension, we showed that cardiac mass is related to arterial elasticity.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Aorta; Aorta, Thoracic; Calcium, Dietary; Cholecalciferol; Data Interpretation, Statistical; Elasticity; Hemodynamics; Hypertension; Hypertrophy, Left Ventricular; Indoles; Male; Nicotine; Perindopril; Placebos; Random Allocation; Rats; Rats, Wistar; Renin; Systole

Although altered cellular calcium handling plays a critical role in the pathophysiology of hypertension, little attention has been focused on the impact of calcium regulating hormones on target-organs (e.g. vascular tissue). Therefore the relationship between calcium, phosphorus, parathyroid hormone, 25- and 1,25-(di) hydroxyvitamin D3, blood pressure (BP) and regional circulation was examined in 25 patients (44 +/- 2.5 years) with moderate hypertension (systolic BP 164 +/- 4 mmHg, diastolic BP 105 +/- 2 mmHg). Calf and finger blood flow were measured simultaneously using ECG-triggered plethysmography at rest and after 3 min arterial occlusion (reactive hyperemia). Systolic and diastolic BP were inversely correlated with 25-hydroxyvitamin D3 (r = -0.511 and r = -0.445, p < 0.002). Calf vascular resistance at rest (r = -0.46, p = 0.02) and after 3 min arterial occlusion (r = -0.78, p = 0.0001) was related to 25-hydroxyvitamin D3 concentration. Only calf vascular resistance during reactive hyperemia was significantly related to 1,25-dihydroxyvitamin D3 (r = -0.44, p = 0.03). After correction for blood pressure calf vascular resistance after 3 min arterial occlusion remained significantly and inversely related with 25-hydroxyvitamin D3. There was no relation between finger (skin) circulation and vitamin D3. All other calcium regulating factors were unrelated to the parameters of peripheral circulation. Our results indicate that among the calcium regulating factors, particularly vitamin D3 seems to inversely influence muscle, but not skin vascular tone-independently of blood pressure in mild to moderate hypertension.

Topics: Adult; Blood Pressure; Calcifediol; Calcitriol; Calcium; Cholecalciferol; Electrocardiography; Female; Humans; Hyperemia; Hypertension; Magnesium; Male; Middle Aged; Muscles; Organ Specificity; Parathyroid Hormone; Phosphorus; Plethysmography; Regional Blood Flow; Skin; Vascular Resistance

According to chemical analyses, the development of conventional human coronary artery plaques from "fatty streaks" to "fibrous plaques" and "complicated lesions" is dominated by progressive mural calcium (Ca) incorporation. The atherogenic significance of Ca ions and arterial Ca overload was examined under the influence of nicotine, oxidatively modified low-density lipoproteins, spontaneous hypertension, and an elevated extracellular Ca concentration or vitamin D3. Experiments were carried out either in vitro on cultured medial cells of rats or in vivo on various types of experimental arteriosclerosis of rats. Suitable Ca antagonists (verapamil, diltiazem, nifedipine, or nitrendipine) prevented experimental Ca overload of arterial walls and transmembrane Ca uptake into cultured medial cells produced by risk factors. Thus they protected, in vivo and/or in vitro, against the atherogenic potential of Ca ions, i.e., migration, proliferation, matrix production and intracellular Ca overload of vascular smooth-muscle cells, as well as calcification of elastic fibers. The data indicate that various Ca-consuming processes demand a progressive uptake of Ca into arterial walls if Ca-dominated types of arteriosclerosis develop. Under experimental conditions, specific Ca antagonists inhibit Ca-mediated arteriosclerotic alterations by preventing progressive mural Ca incorporation.

Topics: Adult; Aged; Aged, 80 and over; Animals; Arteriosclerosis; Calcium; Calcium Channel Blockers; Cells, Cultured; Cholecalciferol; Cholesterol; Coronary Vessels; Diltiazem; Disease Models, Animal; Humans; Hypertension; Middle Aged; Muscle, Smooth, Vascular; Nicotine; Nifedipine; Nitrendipine; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Sprague-Dawley; Risk Factors; Verapamil

1. The diet of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) and Wistar (NWR) rats was supplemented with either 2% calcium lactate in the drinking water or 12.5 micrograms vitamin D3 100 g-1 body weight daily by gavage, for 14 days. 2. The blood pressure of the SHR treated with either calcium or vitamin D decreased to the same levels as that of WKY and NWR. 3. The response to bradykinin of the SHR isolated duodenum, which is predominantly contractile, upon treatment with vitamin D (but not with calcium), became predominantly relaxant, approaching the normal behavior of the WKY and NWR duodenum. 4. The relaxant responses of the SHR and WKY duodenum to potassium were smaller than those of NWR, but treatment with vitamin D increased the response in all three rat strains. 5. It is concluded that, besides sharing the hypotensive effect of calcium, vitamin D treatment of SHR has an effect on the duodenum smooth muscle which might be due to calmodulin-dependent activation of calcium-dependent potassium channels.

Topics: Animals; Blood Pressure; Bradykinin; Cholecalciferol; Duodenum; Female; Hypertension; In Vitro Techniques; Muscle Relaxation; Potassium; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY

Twenty-four children with vitamin D intoxication and a follow-up of one to thirteen years old (means: four years and seven months) are reviewed. Over-dosage was prescribed by medical order in 66.6% of patients and by the mother herself in 16.6%. Intensity of clinical symptoms (renal, neurologic, digestive) were related with daily dose administered whilst final secuelae depends on duration of overdosage. Hipercalcemia was easily corrected by association of low calcium diet, corticoesteroids and/or furosemide in least than a month in 81% of cases. Two patients died during the acute fase and 22.7% remain with permanent damage (five in chronic renal failure, one in haemodialysis and three with low IC).

Topics: Bone Diseases, Metabolic; Calcinosis; Calcium; Child; Child, Preschool; Cholecalciferol; Female; Humans; Hypertension; Infant; Male; Nephrocalcinosis

Topics: Child; Cholecalciferol; Humans; Hypercalcemia; Hypertension; Infant; Kidney Diseases; Rickets

Topics: Cholecalciferol; Female; Humans; Hypertension; Pregnancy; Pregnancy Complications; Vitamin D; Vitamins