The Protective Role of Vitamin C on Endothelial Dysfunction (original) (raw)
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On the Role of Vitamin C and Other Antioxidants in Atherogenesis and Vascular Dysfunction
Proceedings of the Society for Experimental Biology and Medicine, 1999
Oxidative stress has been implicated as an important etiologic factor in atherosclerosis and vascular dysfunction. Antioxidants may inhibit atherogenesis and improve vascular function by two different mechanisms. First, lipid-soluble antioxidants present in low-density lipoprotein (LDL), including ␣-tocopherol, and watersoluble antioxidants present in the extracellular fluid of the arterial wall, including ascorbic acid (vitamin C), inhibit LDL oxidation through an LDL-specific antioxidant action. Second, antioxidants present in the cells of the vascular wall decrease cellular production and release of reactive oxygen species (ROS), inhibit endothelial activation (i.e., expression of adhesion molecules and monocyte chemoattractants), and improve the biologic activity of endothelium-derived nitric oxide (EDNO) through a cell-or tissue-specific antioxidant action. ␣-Tocopherol and a number of thiol antioxidants have been shown to decrease adhesion molecule expression and monocyteendothelial interactions. Vitamin C has been demonstrated to potentiate EDNO activity and normalize vascular function in patients with coronary artery disease and associated risk factors, including hypercholesterolemia, hyperhomocysteinemia, hypertension, diabetes, and smoking.
General Physiology and Biophysics, 2011
The aim of this study was to assess the effects of vitamin C (ascorbic acid) on coronary flow and oxidative stress markers with or without non-specific inhibition of nitric oxide synthase by N ω -nitro-L-arginine monomethyl ester (L-NAME) in isolated rat hearts. The hearts of male Wistar albino rats (n = 12, age 8 weeks, body mass 180-200 g) were retrograde perfused according to the Langendorff technique at gradually increased constant perfusion pressure (40-120 cm H 2 O). Coronary flow, nitrite outflow, superoxide anion production, and index of lipid peroxidation (by measuring thiobarbituric acid reactive substances) in coronary effluent were determined. The experiments were performed during control conditions and in presence of vitamin C (100 µM) alone or vitamin C (100 µM) + L-NAME (30 µM). Administration of vitamin C induced only increase of nitrite levels, while vitamin C + L-NAME induced significant decrease of coronary flow above autoregulatory range, i.e. especially at higher coronary perfusion pressure (CPP) values, accompanied with similar dynamic in nitrite outflow. Vitamin C + L-NAME also induced significant decrease in TBARS production. The results of our study show no significant effects of vitamin C administration either on ROS levels or on coronary flow in isolated rat heart.
American journal of physiology. Heart and circulatory physiology, 2002
High arterial blood oxygen tension increases vascular resistance, possibly related to an interaction between reactive oxygen species and endothelium-derived vasoactive factors. Vitamin C is a potent antioxidant capable of reversing endothelial dysfunction due to increased oxidant stress. We tested the hypotheses that hyperoxic vasoconstriction would be prevented by vitamin C, and that acetylcholine-mediated vasodilation would be blunted by hyperoxia and restored by vitamin C. Venous occlusion strain gauge plethysmography was used to measure forearm blood flow (FBF) in 11 healthy subjects and 15 congestive heart failure (CHF) patients, a population characterized by endothelial dysfunction and oxidative stress. The effect of hyperoxia on FBF and derived forearm vascular resistance (FVR) at rest and in response to intra-arterial acetylcholine was recorded. In both healthy subjects and CHF patients, hyperoxia-mediated increases in basal FVR were prevented by the coinfusion of vitamin C....
Journal of Biological Chemistry, 2007
ance to oxidative stress, 10-times more glutathione than vitamin C was required, (iii) full antioxidant protection required the simultaneous presence of intracellular and extracellular vitamin C at concentrations normally found in vivo, and (iv) intracellular vitamin C cooperated in enhancing glutathione recovery after oxidative challenge thus providing cells with enhanced survival potential, while extracellular vitamin C was recycled through a mechanism involving the simultaneous neutralization of oxidant species. Therefore, in endothelial cells under oxidative challenge, vitamin C functions as an essential cellular antioxidant even in the presence of a vast molar excess of glutathione.
Free Radical Biology and Medicine, 2000
Endothelium-derived nitric oxide (EDNO) is a pivotal molecule in the regulation of vascular tone via the stimulation of vascular smooth muscle cell relaxation and concomitant vasodilation. In addition, EDNO exerts a number of other potent antiatherogenic effects, including inhibition of leukocyte-endothelial interactions, smooth muscle cell proliferation, and platelet aggregation. Endothelial vasodilator dysfunction has been observed in patients with CAD or coronary risk factors such as hypercholesterolemia, hyperhomocysteinemia, essential hypertension, diabetes mellitus, smoking, and aging. Most of these conditions are associated with increased oxidative stress, particularly increased production of superoxide radicals and elevated levels of oxidized LDL, both of which can attenuate the biological activity of EDNO. The levels of superoxide and oxidized LDL can be decreased by administering the small molecule antioxidants vitamins E and C. Vitamin C also spares intracellular thiols, which in turn can stabilize EDNO through the formation of biologically active S-nitrosothiols. Here we review the role that vitamins E and C and thiol compounds play in endothelium-dependent vasodilation. Understanding the mechanisms of the reversal of endothelial dysfunction by natural antioxidants will lead to successful therapeutic interventions of CAD and its clinical sequelae.
Antioxidants and endothelial nitric oxide synthesis
European Journal of Clinical Pharmacology, 2006
Oxidative stress in the vasculature has been suggested to contribute to the development of endothelial dysfunction via different mechanisms including LDL oxidation, nitric oxide (NO) scavenging, or oxidation of tetrahydrobiopterin, a critical cofactor of endothelial NO synthase (eNOS). Antioxidants may interfere with these processes and protect NO formed in the endothelium. In particular, ascorbic acid at high concentrations seems to be a prerequisite for sufficient NO bioavailability. Moreover, there is accumulating evidence that ascorbic acid improves tetrahydrobiopterin availability in the vasculature most probably via recycling oxidized tetrahydrobiopterin back to the fully reduced pterin. In addition, ascorbic acid may reduce the α-tocopheroxyl radical and may be required for beneficial vascular effects of α-tocopherol. Recent data have shown that apart from indirect protection of NO from inactivation, α-tocopherol exerts a direct stimulatory effect on eNOS activation via serine 1177 phosphorylation. This effect was amplified by ascorbic acid suggesting that both compounds may act synergistically in optimizing endothelial NO synthesis. The data obtained in cell culture and animal studies are promising, but human long-term studies are needed to determine whether the described mechanisms are active in vivo and may provide a rationale for optimizing dietary or supplementary intake of antioxidant vitamins in certain subsets of patients.
British Journal of Pharmacology, 1999
Low density lipoprotein (LDL) inhibits endothelium-dependent relaxation. The mechanism is uncertain, but increased production of superoxide anion O 2 7 with inactivation of endothelium-derived NO and formation of toxic free radical species have been implicated. We investigated eects of the cell permeable superoxide dismutase mimetic manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP), the free radical scavenger vitamin C and arginine (which may reduce O 2 7 formation) on acute LDL-induced endothelial dysfunction in rabbit aortic rings, using LDL prepared by ultracentrifugation of plasma from healthy men and aortic rings from New Zealand white rabbits. 2 LDL (150 mg protein ml 71 for 20 min) markedly inhibited relaxation of aortic rings (in Krebs' solution at 378C and pre-constricted to 80% maximum tension with noradrenaline) to acetylcholine 82+10% (mean percentage dierence between sum of relaxations after each concentration of acetylcholine in the presence and absence of LDL, +s.e.mean, n=26, P50.001) but not to the endothelium-independent agonist nitroprusside. 3 MnTMPyP (10 mM) reduced inhibitory eects of LDL from 124+27 to 56+17% (n=6, P50.05). 4 Vitamin C (1 mM) reduced inhibitory eects of LDL from 59+8 to 22+5% (n=6, P50.05). 5 Inhibitory eects of LDL were similar in the absence or presence of arginine (84+12 vs 79+16%, n=14, P=0.55). Eects of L-arginine (10 mM) did not dier signi®cantly from those of D-arginine (10 mM). 6 Acute (20 min) exposure of aortic rings to LDL impairs endothelium-dependent relaxation which can be partially restored by MnTMPyP and vitamin C. This is consistent with LDL causing increased O 2 7 generation.