Ascorbic acid levels and neutrophil superoxide production in blood of pre-, early and late hypertensive stroke-prone spontaneously hypertensive rats

Summary We compared ascorbic acid (AA) levels in the blood and TPA- and fMLP-stimulated superoxide (O(2)(•-)) production in neutrophils of pre-, early, and late hypertensive stroke-prone spontaneously hypertensive rats (SHRSP) with those of age-matched Wistar Kyoto rats (WKY), or two other normotensive strains of rats. Plasma and lymphocyte AA levels were about two-fold higher in…

Plasma vitamin C predicts incident heart failure in men and women in European Prospective Investigation into Cancer and Nutrition-Norfolk prospective study.

Summary Background: Fruit and vegetable intake has been associated with lower risk for cardiovascular risk factors and disease, but data on heart failure are sparse and inconsistent. The association of plasma vitamin C, a biomarker reflecting fruit and vegetable intake, with heart failure has not been studied. Methods: We examined the prospective association of plasma…

Plasma vitamin C level, fruit and vegetable consumption, and the risk of new-onset type 2 diabetes mellitus: the European prospective investigation of cancer–Norfolk prospective study.

Summary Background: Epidemiologic studies suggest that greater consumption of fruit and vegetables may decrease the risk of diabetes mellitus, but the evidence is limited and inconclusive. Plasma vitamin C level is a good biomarker of fruit and vegetable intake, but, to our knowledge, no prospective studies have examined its association with diabetes risk. This study…

Fruit and vegetable consumption and self-reported functional health in men and women in the European Prospective Investigation into Cancer-Norfolk (EPIC-Norfolk): a population-based cross-sectional study.

Summary Objectives: To investigate the association between fruit and vegetable consumption and self-reported physical and mental functional health measured by an anglicised short-form 36-item questionnaire (UK SF-36). Design: Population-based cross-sectional study. Setting: General community in Norfolk, UK. Subjects: A total of 16,792 men and women aged 40-79 years recruited from general practice population registers as…

Plasma vitamin C and risk of hospitalisation with diagnosis of atrial fibrillation in men and women in EPIC-Norfolk prospective study.

Summary Background: Fruit and vegetable intake has been associated with lower risk for cardiovascular risk factors and disease. Data on its association with atrial fibrillation are lacking. Methods and results: We examined the prospective association of plasma vitamin C concentration as a biomarker for fruit and vegetable intake with the risk of hospitalisation with diagnosis…

Association between plasma vitamin C concentrations and blood pressure in the European prospective investigation into cancer-Norfolk population-based study

Summary The effect of fruit and vegetable consumption and blood pressure is unclear. A population-based cross-sectional study was conducted in 20 926 men and women aged 40 to 79 years participating in the European Prospective Investigation Into Cancer-Norfolk who completed a health questionnaire and attended a clinic from 1993 to 1997. The relationship between plasma…

Increased oxidative stress is responsible for severer cerebral infarction in stroke-prone spontaneously hypertensive rats

Summary Aims: To examine the role of increased oxidative stress in the pathogenesis of cerebral infarction in stroke in stroke-prone spontaneously hypertensive rats (SHR-SP). Methods: The differentially expressed brain protein profile was examined in spontaneously hypertensive rats (SHR) (control group) and SHR-SP using two-dimensional fluorescent difference gel electrophoresis (2D-DIGE). In addition, oxidative stress indicators including…

Effects of ascorbic acid on impaired vascular reactivity in aortas isolated from age-matched hypertensive and diabetic rats

Summary Impaired vascular reactivity is a hallmark of several cardiovascular diseases that include hypertension and diabetes. This study compared the changes in vascular reactivity in age-matched experimental hypertension and diabetes, and, subsequently, tested whether these changes could be affected directly by ascorbic acid (10 microM). Endothelium-derived nitric oxide (NO) modulation of ascorbic acid effects was…

Ascorbic acid prevents cigarette smoke injury to endothelium-dependent arterial relaxation

Summary Background: Arterial endothelium-dependent acetylcholine relaxation is impaired by smoking, and this injury may be mediated by oxygen free radicals. The purpose of this study was to examine the effect of ascorbic acid (AA) treatment on this injury. Materials and methods: New Zealand White rabbits (n = 6, each group) were placed in a 240-ft3…

Tetrahydrobiopterin, L-arginine and vitamin C actsynergistically to decrease oxidative stress, increase nitricoxide and improve blood flow after induction of hindlimbischemia in the rat.

Summary Nitric oxide (NO) derived from endothelial nitric oxide synthase (eNOS) is a potent vasodilator and signaling molecule that plays an essential role in vascular remodeling of collateral arteries and perfusion recovery in response to hindlimb ischemia. In ischemic conditions, decreased NO bioavailability was observed because of increased oxidative stress, decreased L-arginine and tetrahydrobiopterin. This…

Vitamin C improves the effect of a new nitric oxide donor on the vascular smooth muscle from renal hypertensive rats

Summary Impaired relaxation induced by the new nitric oxide (NO) donor [Ru(NH.NHq)(terpy)NO(+)](3+) (TERPY) has been observed in the aortic rings from renal hypertensive rats (2K-1C). An increased production of reactive oxygen species (ROS) in the aortas from 2K-1C rats are capable of reducing NO bioavailability. Therefore, this study aimed at investigating the effects of an…

Lipoic acid and vitamin C potentiate nitric oxide synthesis in human aortic endothelial cells independently of cellular glutathione status

Summary Vitamin C and thiol agents improve vasomotor function. To determine whether these compounds directly affect endothelial function, nitric oxide (NO) synthesis was measured in human aortic endothelial cells treated with ascorbic acid or the thiol modulating agents lipoic acid or L-2-oxothiazolidine-4-carboxylic acid (OTC). A dose-dependent increase in A23187-stimulated NO synthesis and elevated cGMP levels…

N-acetylcysteine decreases angiotensin II receptor binding in vascular smooth muscle cells.

Summary Antioxidants seem to inhibit angiotensin II (Ang II) actions by consuming stimulated reactive oxygen species. An alternative hypothesis was investigated: Antioxidants that are also strong reducers of disulfide bonds inhibit the binding of Ang II to its surface receptors with consequent attenuation of signal transduction and cell action. Incubation of cultured vascular smooth muscle…

Association between Serum Vitamin C and the Blood Pressure: A Systematic Review and Meta-Analysis of Observational Studies

Summary Background: Hypertension is regarded as a major and independent risk factor of cardiovascular diseases, and numerous studies observed an inverse correlation between vitamin C intake and blood pressure. Aim: Our aim is to investigate the relationship between serum vitamin C and blood pressure, including the concentration differences and the correlation strength. Method: Two independent…

Plasma vitamin C modifies the association between hypertension and risk of stroke

Summary Background and purpose: There are no prospective studies to determine whether plasma vitamin C modifies the risk of stroke among hypertensive and overweight individuals. We sought to examine whether plasma vitamin C modifies the association between overweight and hypertension and the risk of stroke in middle-aged men from eastern Finland. Methods: We conducted a…

Plasma Ascorbic Acid, A Priori Diet Quality Score, and Incident Hypertension: A Prospective Cohort Study.

Summary Vitamin C may reduce risk of hypertension, either in itself or by marking a healthy diet pattern. We assessed whether plasma ascorbic acid and the a priori diet quality score relate to incident hypertension and whether they explain each other’s predictive abilities. Data were from 2884 black and white adults (43% black, mean age…

Effects of vitamin C stimulation on rehabilitation of dysphagia after stroke: a randomized trial

Summary Background: Stroke is a clinical syndrome of localized or global brain dysfunction caused by cerebrovascular disease. Aim: The aim of this study was to explore the effect of vitamin C acid stimulation on the rehabilitation process, Nourishment State Index and immune function indicators of stroke patients with dysphagia. Design: This is a prospective cohort…

Ascorbic acid status and subsequent diastolic and systolic blood pressure

Summary Free radicals and oxidation are involved in several aspects of blood pressure physiology. We investigated the relationship between blood pressure and antioxidants, including plasma ascorbic acid (AscA), in a 17-week controlled-diet study. Study subjects included 68 men aged 30 to 59 years who had a mean diastolic blood pressure of 73.4 mm Hg and…

Coronary vasoregulation in patients with various risk factors in response to cold pressor testing: contrasting myocardial blood flow responses to short- and long-term vitamin C administration

Summary Objectives: We sought to determine whether abnormal myocardial blood flow (MBF) responses to the cold pressor test (CPT) in patients with various risk factors may involve different mechanisms that could lead to varying responses of short- and long-term administration of antioxidants. Background: There is a growing body of evidence that increased vascular production of…

Plasma vitamin C concentrations predict risk of incident stroke over 10 y in 20 649 participants of the European Prospective Investigation into Cancer Norfolk prospective population study

Summary Background: The relation between plasma vitamin C and risk of stroke remains unclear. Although clinical trials showed no significant benefit of vitamin C supplementation in reducing stroke risk, they were not able to examine the relation between plasma vitamin C concentrations and stroke risk in a general population. Objective: The objective was to examine…

Reversible pulmonary hypertension associated with vitamin C deficiency

Summary We describe the case of a 40-year-old female patient who developed severe pulmonary hypertension and life-threatening right-sided heart failure in association with dietary scurvy and iron deficiency. Supplementation with oral vitamin C and iron very likely contributed to her complete cure. Scurvy-associated pulmonary arterial hypertension could result from impaired availability of endothelial nitric oxide,…

Lower antioxidant vitamins (A, C and E) and trace minerals (Zn, Cu, Mn, Fe And Se) status in patients with cerebrovascular disease

Summary The management of antioxidant micronutrient status in patients with chronic diseases may be an important step in controlling disease progression and preventing deterioration in patient quality of life. The objective of this study was to investigate the antioxidant micronutrient status and lipid profiles of cerebrovascular disease (CbVD) patients and to compare this information with…

Vitamin C improves attenuated angiotensin II-induced endothelium-dependent vasodilation in human forearm vessels

Summary Endothelial dysfunction might be related to an increase in superoxide anion production in patients with hypertension, hypercholesterolemia, diabetes mellitus, and heart failure. Studies in animal models indicate that angiotensin II increases superoxide anion production by vascular tissues. We examined whether angiotensin II attenuates endothelium-dependent vasodilation via an increase in superoxide anion production in human…

Urine metabolomics signatures in reversible cerebral vasoconstriction syndrome

Summary Background: The pathophysiology of reversible cerebral vasoconstriction syndrome is unclear. An unbiased systems-based approach might help to illustrate the metabolite profiling and underlying pathophysiology. Methods: Urine samples were collected from reversible cerebral vasoconstriction syndrome patients and matched controls recruited in Taipei Veterans General Hospital. 1H-Nuclear magnetic resonance was used to initially explore the metabolic…

Oxidative stress and increased formation of vasoconstricting F2-isoprostanes in patients with reversible cerebral vasoconstriction syndrome

Summary The pathophysiology of reversible cerebral vasoconstriction syndrome (RCVS) is unknown. Oxidative stress is detrimental to endothelial function and vascular reactivity. We hypothesized that the oxidative stress marker 8-iso-prostaglandin F2α, which is also a potent vasoconstrictor, might contribute to the pathogenesis of RCVS. Recruited participants included 103RCVS patients, 53 patients with primary headache with acute…

L-Ascorbic acid potentiates nitric oxide synthesis in endothelial cells

Summary Ascorbic acid has been shown to enhance impaired endothelium-dependent vasodilation in patients with atherosclerosis by a mechanism that is thought to involve protection of nitric oxide (NO) from inactivation by free oxygen radicals. The present study in human endothelial cells from umbilical veins and coronary arteries investigates whether L-ascorbic acid additionally affects cellular NO…

Vitamin C in plasma is inversely related to blood pressure and change in blood pressure during the previous year in young Black and White women

Summary Background: The prevalence of hypertension and its contribution to cardiovascular disease risk makes it imperative to identify factors that may help prevent this disorder. Extensive biological and biochemical data suggest that plasma ascorbic acid may be such a factor. In this study we examined the association between plasma ascorbic acid concentration and blood pressure…

Long-term vitamin C treatment increases vascular tetrahydrobiopterin levels and nitric oxide synthase activity

Summary In cultured endothelial cells, the antioxidant, L-ascorbic acid (vitamin C), increases nitric oxide synthase (NOS) enzyme activity via chemical stabilization of tetrahydrobiopterin. Our objective was to determine the effect of vitamin C on NOS function and tetrahydrobiopterin metabolism in vivo. Twenty-six to twenty-eight weeks of diet supplementation with vitamin C (1%/kg chow) significantly increased…

Vitamin C and Cardiovascular Disease: An Update

Summary The potential beneficial effects of the antioxidant properties of vitamin C have been investigated in a number of pathological conditions. In this review, we assess both clinical and preclinical studies evaluating the role of vitamin C in cardiac and vascular disorders, including coronary heart disease, heart failure, hypertension, and cerebrovascular diseases. Pitfalls and controversies…

The role of cellular micronutrient analysis, nutraceuticals, vitamins, antioxidants and minerals in the prevention and treatment of hypertension and cardiovascular disease.

Summary Macronutrient and micronutrient deficiencies are very common in the general population and may be even more common in patients with hypertension and cardiovascular disease due to genetic, environmental causes and prescription drug use. The Hypertension Institute in Nashville, TN, has evaluated micronutrient deficiencies and oxidation status, in a group of hypertensive versus normotensive patients.…

Vitamin C prevents stress-induced damage on the heart caused by the death of cardiomyocytes, through down-regulation of the excessive production of catecholamine, TNF-α, and ROS production in Gulo(-/-)Vit C-Insufficient mice.

Summary It is thought that vitamin C has protective roles on stress-induced heart damage and the development of cardiovascular diseases, but its precise role and mechanisms are unclear. In the present study, we investigated the specific mechanisms by which vitamin C leads to protecting the heart from stress-induced damage in the Gulo(-/-) mice which cannot…

Elevated oxidative stress and sensorimotor deficits but normal cognition in mice that cannot synthesize ascorbic acid.

Summary Oxidative stress is implicated in the cognitive deterioration associated with normal aging as well as neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. We investigated the effect of ascorbic acid (vitamin C) on oxidative stress, cognition, and motor abilities in mice null for gulono-γ-lactone oxidase (Gulo). Gulo−/− mice are unable to synthesize ascorbic acid…

The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review).

Summary The concept of mild chronic vascular inflammation as part of the pathophysiology of cardiovascular disease, most importantly hypertension and atherosclerosis, has been well accepted. Indeed there are links between vascular inflammation, endothelial dysfunction and oxidative stress. However, there are still gaps in our understanding regarding this matter that might be the cause behind disappointing…

Ascorbic Acid Protects against Hypertension through Downregulation of ACE1 Gene Expression Mediated by Histone Deacetylation in Prenatal Inflammation-Induced Offspring

Summary Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Prenatal exposure to lipopolysaccharide (LPS) leads to hypertension in a rat offspring. However, the mechanism is still unclear. This study unraveled epigenetic mechanism for this and explored the protective effects of ascorbic acid against hypertension on prenatal inflammation-induced offspring. Prenatal LPS exposure resulted…

Vitamin C deficiency induces hypoglycemia and cognitive disorder through S-nitrosylation-mediated activation of glycogen synthase kinase 3β.

Summary Vitamin C (VC, l-ascorbic acid) is an essential nutrient that plays a key role in metabolism and functions as a potent antioxidant in regulating the S-nitrosylation and denitrosylation of target proteins. The precise function of VC deprivation in glucose homeostasis is still unknown. In the absence of L-gulono-1,4-lactone oxidoreductase, an essential enzyme for the…

Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin

Summary Ascorbic acid enhances NO bioactivity in patients with vascular disease through unclear mechanism(s). We investigated the role of intracellular ascorbic acid in endothelium-derived NO bioactivity. Incubation of porcine aortic endothelial cells (PAECs) with ascorbic acid produced time- and dose-dependent intracellular ascorbic acid accumulation that enhanced NO bioactivity by 70% measured as A23187-induced cGMP accumulation.…

Nutrient-Derived Beneficial for Blood Pressure Dietary Pattern Associated with Hypertension Prevention and Control: Based on China Nutrition and Health Surveillance 2015-2017.

Summary Background: Greater adherence of Dietary Approach to Stop Hypertension (DASH) or the Mediterranean dietary pattern were reported to be beneficial for blood pressure. However, both were established based on Western populations. Our current study aimed to explore a dietary pattern which might be suitable for hypertension prevention and control among Chinese adults nationwide. Methods:…

L-ascorbic acid potentiates endothelial nitric oxide synthesis via a chemical stabilization of tetrahydrobiopterin

Summary Ascorbic acid has been shown to stimulate endothelial nitric oxide (NO) synthesis in a time- and concentration-dependent fashion without affecting NO synthase (NOS) expression or l-arginine uptake. The present study investigates if the underlying mechanism is related to the NOS cofactor tetrahydrobiopterin. Pretreatment of human umbilical vein endothelial cells with ascorbate (1 microm to…

Ascorbic acid status and subsequent diastolic and systolic blood pressure

Summary Free radicals and oxidation are involved in several aspects of blood pressure physiology. We investigated the relationship between blood pressure and antioxidants, including plasma ascorbic acid (AscA), in a 17-week controlled-diet study. Study subjects included 68 men aged 30 to 59 years who had a mean diastolic blood pressure of 73.4 mm Hg and…

Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension

Summary Background: Essential hypertension is associated with impaired endothelium-dependent vasodilation. Inactivation of endothelium-derived nitric oxide by oxygen free radicals participates in endothelial dysfunction in experimental hypertension. To test this hypothesis in humans, we evaluated the effect of antioxidant vitamin C on endothelium-dependent responses in essential hypertensive patients. Methods and results: In 14 healthy subjects (47.1+/-4.8…

Vitamin C improves endothelial dysfunction of epicardial coronary arteries in hypertensive patients

Summary Background: There is evidence for increased formation of free radicals in patients with hypertension, raising the possibility that NO is inactivated by free radicals, which impairs coronary endothelial function. Therefore, we tested the hypothesis that the antioxidant vitamin C could improve abnormal endothelial function of coronary arteries in patients with hypertension. Methods and results:…

Ascorbic acid improves brachial artery vasodilation during progressive handgrip exercise in the elderly through a nitric oxide-mediated mechanism

Summary The proposed mechanistic link between the age-related attenuation in vascular function and free radicals is an attractive hypothesis; however, direct evidence of free radical attenuation and a concomitant improvement in vascular function in the elderly is lacking. Therefore, this study sought to test the hypothesis that ascorbic acid (AA), administered intra-arterially during progressive handgrip…

Acute ascorbic acid ingestion increases skeletal muscle blood flow and oxygen consumption via local vasodilation during graded handgrip exercise in older adults

Summary Human aging is associated with reduced skeletal muscle perfusion during exercise, which may be a result of impaired endothelium-dependent dilation and/or attenuated ability to blunt sympathetically mediated vasoconstriction. Intra-arterial infusion of ascorbic acid (AA) increases nitric oxide-mediated vasodilation and forearm blood flow (FBF) during handgrip exercise in older adults, yet it remains unknown whether…

Tetrahydrobiopterin, L-arginine and vitamin C act synergistically to decrease oxidant stress and increase nitric oxide that increases blood flow recovery after hindlimb ischemia in the rat

Summary Nitric oxide (NO) derived from endothelial nitric oxide synthase (eNOS) is a potent vasodilator and signaling molecule that plays essential roles in neovascularization. During limb ischemia, decreased NO bioavailability occurs secondary to increased oxidant stress, decreased L-arginine and tetrahydrobiopterin. This study tested the hypothesis that dietary cosupplementation with tetrahydrobiopterin (BH4), L-arginine and vitamin C…

The acute effect of high-dose intravenous vitamin C and other nutrients on blood pressure: a cohort study

Summary Background: Regular intake of vitamin C/ascorbate reduces blood pressure (BP) in hypertensives. High-dose intravenous vitamin C (IVC) achieves higher plasma levels; however, there is a paucity of research on acute BP effects. Our study is the first to investigate the effect of high-dose IVC, with or without concomitant i.v. nutrients, on BP during i.v.…

Oxidative stress-induced dysregulation of arteriolar wall shear stress and blood pressure in hyperhomocysteinemia is prevented by chronic vitamin C treatment

Summary We aimed to test the hypothesis that an enhanced level of reactive oxygen species (ROS) is primarily responsible for the impairment of nitric oxide (NO)-mediated regulation of arteriolar wall shear stress (WSS) in hyperhomocysteinemia (HHcy). Thus flow/WSS-induced dilations of pressurized gracilis muscle arterioles (basal diameter: approximately 170 microm) isolated from control (serum Hcy: 6…

Supplementation with vitamins C and E improves arterial stiffness and endothelial function in essential hypertensive patients.

Summary Background: Essential hypertension is characterized by endothelial dysfunction, arterial stiffness, and increased oxidative stress. We evaluated the effect of short-term combined treatment with the antioxidants vitamins C and E on endothelial function, arterial stiffness, and oxidative stress in untreated essential hypertensive patients. Methods: A randomized, double-blind, placebo-controlled, crossover study design was used to assign…

Effect of ascorbic acid on endothelial dysfunction of epicardial coronary arteries in chronic smokers assessed by cold pressor testing

Summary Background: In chronic smokers there is evidence for increased formation of oxygen-derived free radicals within the vessel wall impairing endothelial function. It has been suggested that the inactivation of endothelium-derived nitric oxide by oxygen free radicals contributes to endothelial dysfunction. Hence, we tested the hypothesis that in chronic smokers the antioxidant ascorbic acid could…