ascorbic-acid and Hypotension

Bacterial bloodstream infection causes septic syndromes that range from systemic inflammatory response syndrome (SIRS) and encephalopathy to severe sepsis and septic shock. Microvascular dysfunction, comprising impaired capillary blood flow and arteriolar responsiveness, precedes multiple organ failure. Vitamin C (ascorbate) levels are low in critically ill patients. The impact of ascorbate administered orally is moderate because of its limited bioavailability. However, intravenous injection of ascorbate raises plasma and tissue concentrations of the vitamin and may decrease morbidity. In animal models of polymicrobial sepsis, intravenous ascorbate injection restores microvascular function and increases survival. The protection of capillary blood flow and arteriolar responsiveness by ascorbate may be mediated by inhibition of oxidative stress, modulation of intracellular signaling pathways, and maintenance of homeostatic levels of nitric oxide. Ascorbate scavenges reactive oxygen species (ROS) and also inhibits the NADPH oxidase that synthesizes superoxide in microvascular endothelial cells. The resulting changes in redox-sensitive signaling pathways may diminish endothelial expression of inducible nitric oxide synthase (iNOS), tissue factor and adhesion molecules. Ascorbate also regulates nitric oxide concentration by releasing nitric oxide from adducts and by acting through tetrahydrobiopterin (BH4) to stimulate endothelial nitric oxide synthase (eNOS). Therefore, it may be possible to improve microvascular function in sepsis by using intravenous vitamin C as an adjunct therapy.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain Diseases; Humans; Hypotension; Regional Blood Flow; Sepsis

To investigate the roles of epithelial-dendritic cell transformation (EDT) characterized by the expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) in the occurrence of tissue inflammation induced by hemorrhagic hypotension (HH), the protective effect of vitamin C (VitC), and the potential mechanisms.. We conducted an in vitro study using the rat intestinal epithelial cells (IEC-6). After hypoxic culture with or without VitC for 2, 6, 24, and 48 h (n = 3 per group), the expression levels of DC-SIGN, E-cadherin, and Glycogen synthase kinase-3β-S9 (GSK-3β-S9) in IEC-6 cells, IL-1β, and IL-6 concentrations in the cell culture medium were measured. To investigate the potential mechanism, we inhibited E-cadherin expression by siRNA and GSK-3β activity by TDZD-8, respectively. The in vivo study was conducted by establishing SD rat HH model. We observed the expression levels and location of DC-SIGN in the intestines. We also showed histological damage, TNF-α and IL-6 concentrations, and organ injury scores at 2, 6, and 24 h after HH (n = 6 per group), with or without VitC pretreatment.. Hypoxia-induced DC-SIGN expression in IEC-6 cells in a time-dependent manner and the inflammatory factors were also increased. VitC inhibited all these phenomena. Hypoxia inhibited GSK-3β activity and E-cadherin expression. VitC could ease these inhibitions. The inhibitory effect of VitC on DC-SIGN was diminished when E-cadherin expression was inhibited in advance. TDZD-8 diminished the protective effect of VitC on E-cadherin and abolished inhibitory effect of VitC on DC-SIGN expression. HH-induced DC-SIGN expression in rat intestine epithelial cells and the histological damage scores and pro-inflammatory cytokine levels were also increased.. HH induces EDT in rat intestine epithelial cells. VitC maintains GSK-3β activity, attenuates the suppression of E-cadherin caused by hypoxia, and ultimately decreases DC-SIGN expression.

Topics: Animals; Ascorbic Acid; Cadherins; Cell Adhesion Molecules; Cell Hypoxia; Cell Transdifferentiation; Cells, Cultured; Dendritic Cells; Epithelial Cells; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hemodynamics; Hemorrhage; Hypotension; Inflammation Mediators; Intestinal Mucosa; Lectins, C-Type; Male; Rats, Sprague-Dawley; Receptors, Cell Surface; Resuscitation; Systemic Inflammatory Response Syndrome

Naphthalene, a widely used industrial and household chemical, has rarely been an agent of poisoning worldwide. Severe haemolysis from naphthalene poisoning is rare and can be a challenge to clinicians. We report a 22-year-old female, who accidentally ingested naphthalene mixed coconut oil and got admitted with recurrent vomiting, headache and passage of dark urine. Severe intravascular haemolysis with hypotension and neutrophilic leukocytosis was detected. She was treated with red blood cell transfusions, intravenous saline infusion and ascorbic acid.

Topics: Administration, Oral; Anemia, Hemolytic; Ascorbic Acid; Coconut Oil; Erythrocyte Transfusion; Female; Glucose; Hemoglobinuria; Hemolysis; Humans; Hypotension; Infusions, Intravenous; Methemoglobinemia; Naphthalenes; Plant Oils; Poisoning; Severity of Illness Index; Treatment Outcome; Young Adult

The nucleus tractus solitarius (NTS), a major hindbrain area involved in cardiovascular regulation, receives primary afferent fibers from peripheral baroreceptors and chemoreceptors. Hydrogen peroxide (H(2)O(2)) is a relatively stable and diffusible reactive oxygen species (ROS), which acting centrally, may affect neural mechanisms. In the present study, we investigated effects of H(2)O(2) alone or combined with the glutamatergic antagonist kynurenate into the NTS on mean arterial pressure (MAP) and heart rate (HR). Conscious or anesthetized (urethane and alpha-chloralose) male Holtzman rats (280-320 g) were used. Injections of H(2)O(2) (125 to 1500 pmol/40 nl) into the intermediate NTS of anesthetized rats evoked dose-dependent and transient hypotension (-18 +/- 3 to -55 +/- 11 mmHg) and bradycardia (-16 +/- 5 to -116 +/- 40 bpm). Injection of the catalase inhibitor 3-amino-1,2,4-triazole (100 nmol/40 nl) into the NTS also produced hypotension and bradycardia. Previous injection of the ionotropic L-glutamate receptor antagonist kynurenate (7 nmol/40 nl) attenuated by 48% the bradycardic response, without changing the hypotension evoked by H(2)O(2) (500 pmol/40 nl) in anesthetized rats. The antioxidant L-ascorbate (600 pmol/80 nl) injected into the NTS attenuated the bradycardic (42%) and hypotensive (67%) responses to H(2)O(2) (500 pmol/40 nl) into the NTS. In conscious rats, injection of H(2)O(2) (50 nmol/100 nl) into the NTS also evoked intense bradycardia (-207 +/- 8 bpm) and hypotension (-54 +/- 6 mmHg) that were abolished by prior injection of kynurenate (7 nmol/100 nl). The results show that H(2)O(2) into the NTS induces hypotension and bradycardia probably due to activation of glutamatergic mechanisms.

Topics: Amitrole; Anesthesia; Animals; Ascorbic Acid; Blood Pressure; Bradycardia; Cardiovascular System; Chloralose; Excitatory Amino Acid Antagonists; Glutamic Acid; Heart Rate; Hydrogen Peroxide; Hypotension; Kynurenic Acid; Male; Rats; Rats, Sprague-Dawley; Solitary Nucleus; Urethane

The combined effect of traumatic brain injury (TBI) and secondary insult on biochemical changes of cerebral tissue is not well known. For this purpose, we studied the time-course changes of parameters reflecting ROS-mediated oxidative stress and modifications of cell energy metabolism determined in rats subjected to cerebral insult of increasing severity.. Rats were divided into four groups: 1) sham-operated, 2) subjected to 10 minutes of hypoxia and hypotension (HH), 3) subjected to severe diffuse TBI, and 4) subjected to severe diffuse TBI + HH. Rats were killed at different times after injury, and analyses of malondialdehyde, ascorbate, high-energy phosphates, nicotinic coenzymes, oxypurines, nucleosides, and N-acetylaspartate (NAA) were made by high-performance liquid chromatography on whole-brain tissue extracts.. Data indicated a close relationship between degree of oxidative stress and severity of brain insult, as evidenced by the highest malondialdehyde values and lowest ascorbate levels in rats subjected to TBI + HH. Similarly, modifications of parameters related to cell energy metabolism were modulated by increasing severity of brain injury, as demonstrated by the lowest values of energy charge potential, nicotinic coenzymes, and NAA and the highest levels of oxypurines and nucleosides recorded in TBI + HH rats. Both the intensity of oxidative stress-mediated cerebral damage and perturbation of energy metabolism were minimally affected in rats subjected to HH only.. These results showed that the severity of brain insult can be graded by measuring biochemical modifications, specifically, reactive oxygen species-mediated damage, energy metabolism depression, and NAA, thereby validating the rodent model of closed-head diffuse TBI coupled with HH and proposing NAA as a marker with diagnostic relevance to monitor the metabolic state of postinjured brain.

Topics: Animals; Ascorbic Acid; Aspartic Acid; Biomarkers; Brain; Brain Chemistry; Brain Injuries; Chromatography, High Pressure Liquid; Energy Metabolism; Head Injuries, Closed; Hypotension; Hypoxia; Male; Malondialdehyde; NAD; NADP; Nucleosides; Oxidative Stress; Phosphates; Purines; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species

Few studies have examined the effect of acute pressure overload on endothelial function in the coronary microcirculation.. In instrumented conscious dogs with heart rate held constant, veratrine caused a cholinergic nitric oxide (NO)-dependent increase in coronary blood flow by 23+/-3 mL/min (Bezold-Jarisch reflex). Ten minutes after release of constriction of the ascending aorta to increase left ventricular (LV) systolic pressure to 214+/-5 mm Hg for 30 minutes, the veratrine-induced increase in coronary blood flow (7+/-1 mL/min) was reduced by 66% and remained depressed for 2 hours (ie, endothelial stunning [ES]). Nitrite production from isolated coronary microvessels during ES was not different from normal. Ascorbic acid (AA), losartan, or apocynin prevented ES. Myocardial oxygen consumption (MVO2) of LV tissue was measured in vitro in response to bradykinin with preincubation of angiotensin II for 30 minutes. Bradykinin (10(-4) mol/L)-induced reduction in MVO2 was reversed in a concentration-dependent manner by angiotensin II (38+/-1% versus 19+/-2% at 10(-8) mol/L) and restored by coincubation of AA (37+/-2%), tempol (33+/-2%), losartan (34+/-2%), or apocynin (36+/-1%). Exogenous NO-induced reduction in MVO2 was not altered by angiotensin II. Angiotensin II increased lucigenin-detectable superoxide anion in LV tissue in a manner that was inhibited by bradykinin, AA, tempol, losartan, or apocynin.. Endothelial stunning is caused by oxidant processes inhibited by ascorbate, and the activation of NAD(P)H oxidase by increased angiotensin II plays an important role in this process.

Topics: Acetophenones; Angiotensin II; Animals; Ascorbic Acid; Bradycardia; Bradykinin; Coronary Circulation; Cyclic N-Oxides; Dogs; Hypotension; Ligation; Losartan; Myocardial Stunning; Nitric Oxide; Oxidative Stress; Pressure; Reflex; Spin Labels; Superoxides; Veratrine

Topics: Adolescent; Amobarbital; Ascorbic Acid; Boric Acids; Dopamine; Drug Combinations; Female; France; Humans; Hypotension

In pentobarbital anaesthetized rats the intravenous administration of the oligopeptide N-formyl-Met-Leu-Phe (FMLP) is shown to produce a short-lasting hypotension. When the animals have been pretreated with indomethacin, FMLP induces a marked and sustained blood pressure fall. This exaggerated hypotensive response to FMLP is absent in rats which have received a low dose of endotoxin at the day before, and is greatly reduced in animals treated with ascorbic acid or dimethylsulfoxide. In addition, the duration of hypotension is shortened in rats which have been partially depleted of leukocytes by daily methotrexate dosages, or which simultaneously receive drug treatments known to enhance vessel wall cyclic AMP levels like isoprenaline, glucagon or theophylline. The results suggest that after the FMLP administration toxic oxygen species generated by leukocytes contribute to the development of the cardiovascular dysfunction. Endothelial cAMP is suggested to control the sensitivity of the cardiovascular system to these reactive species.

Topics: Animals; Ascorbic Acid; Blood Pressure; Dimethyl Sulfoxide; Endotoxins; Female; Glucagon; Hypotension; Ibuprofen; Indomethacin; Isoproterenol; N-Formylmethionine Leucyl-Phenylalanine; Oxygen; Rats; Rats, Inbred Strains; Theophylline

Topics: Aged; Ascorbic Acid; Blood Pressure Determination; Dipyridamole; Female; Head; Humans; Hypotension; Hypotension, Controlled; Male; Methods; Middle Aged; Neck; Nicotinic Acids; Oxygen Consumption; Oxygen Inhalation Therapy; Regional Blood Flow; Thiamine; Time Factors

Topics: Acid-Base Equilibrium; Acidosis; Administration, Oral; Animals; Aqueous Humor; Ascorbic Acid; Bicarbonates; Chronic Disease; Glaucoma; Humans; Hydrogen-Ion Concentration; Hypotension; Intraocular Pressure; Osmosis; Rabbits

Topics: Adenosine Triphosphate; Adult; Ascorbic Acid; Estrogens; Female; Glucose; Humans; Hypotension; Pregnancy; Sodium Chloride; Thiamine; Uterine Inertia

Topics: Ascorbic Acid; Aspirin; Brain Concussion; Cerebral Ventriculography; Cortisone; Diphenhydramine; Electroencephalography; Headache; Hematoma, Subdural; Histamine H1 Antagonists; Humans; Hypotension; Injections, Intravenous; Procaine; Radiography; Spinal Puncture; Thiamine; Unconsciousness; Vision Disorders; Vitamin B 12

Topics: Ascorbic Acid; Exercise Therapy; Humans; Hypotension; Outpatient Clinics, Hospital; Outpatients; Thiamine

Topics: Ascorbic Acid; Autonomic Nervous System; Autonomic Nervous System Diseases; Central Nervous System Stimulants; Folic Acid; Humans; Hypotension; Vitamin B Complex; Vitamins

Topics: Animals; Ascorbic Acid; Blood Volume; Burns; Diuretics; Dogs; Hypotension; Vitamins