Ascorbate Prevents the Interaction of Superoxide and Nitric Oxide Only at Very High Physiological Concentrations

Abstract

Abstract-The bioactivity of nitric oxide (Y NO) depends, in part, on its interaction with superoxide. Usually, superoxide dismutase (SOD) preserves Y NO bioactivity by limiting the availability of superoxide. Ascorbic acid also effectively scavenges superoxide, but the extent to which this interaction is necessary for intact Y NO bioactivity is not known. Therefore, the present study examined the effect of ascorbic acid on Y NO bioactivity with isolated rabbit arterial segments. A steady flux of superoxide (1.15 to 2.3 mol ⅐ L Ϫ1 ⅐ min Ϫ1 ) produced either by pyrogallol autoxidation or a hypoxanthine/xanthine oxidase system inhibited endothelium-derived Y NO-mediated arterial relaxation elicited by acetylcholine. This effect of superoxide was completely blocked by SOD (300 IU/mL) and the manganese SOD mimic EUK-8 (300 mol/L) and partially inhibited by ascorbic acid (10 mmol/L). Lower concentrations of ascorbic acid were ineffective despite scavenging Ͼ90% of superoxide. We increased the endogenous flux of superoxide (3.2Ϯ0. Key Words: antioxidant Ⅲ free radical Ⅲ blood vessel Ⅲ oxidant Ⅲ peroxynitrite N ormal vascular homeostasis depends on endothelial elaboration of paracrine factors that prevent both platelet adhesion to the endothelial surface and inappropriate vasospasm. One important endothelial product responsible for these functions is nitric oxide ( Y NO), 1 a free radical produced constitutively by the vascular endothelium. Abnormalities in Y NO action and metabolism are known to develop in association with vascular disease and have been implicated in the development of clinically significant vascular events.

Central Infusion of L-Arginine or Superoxide Dismutase Does Not Alter Arterial Pressure in SHR.

“…Superoxide production is reported to be increased in stroke-prone SHR (14), and the physiological action of NO might be counteracted by superoxide even if NOS activity is augmented (23). Inhibition of the production of superoxide by ascorbate or other antioxidant agents improves endothelial function (24). Schnackenberg et al have reported that the renal excretion of 8-iso prostaglandin F2a, which is formed from the attack of superoxide radicals on arachidonic acid and, therefore, is a marker of oxidative stress in vivo, is reduced in tempol-treated SHR (25).…”

Ascorbic acid improves the intrahepatic endothelial dysfunction of patients with cirrhosis and portal hypertension

“…This prevents NO scavenging by ROS, increasing NO bioavailability. 23,24 The aim of this study was to investigate whether ascorbic acid administration might improve hepatic endothelial dysfunction and attenuate the postprandial increase in portal pressure in patients with cirrhosis and portal hypertension.…”

Inflammation in the vascular bed: Importance of vitamin C

“…Regarding the latter effect, reaction of superoxide with cell-derived nitric oxide generates peroxynitrite, a strong and damaging oxidant (Beckman & Koppenol, 1996). As noted previously, relatively high ascorbate concentrations (>100 μM) are required to prevent the reaction of superoxide with nitric oxide (Jackson et al, 1998). Nonetheless, since low millimolar ascorbate concentrations are likely to be present in endothelial cells, ascorbate is probably an effective intracellular scavenger of superoxide.…”

“…Within the cell, the major radical byproduct of mitochondrial oxygen metabolism is superoxide. Although ascorbate concentrations of 100 μM and higher are required to appreciably scavenge superoxide (Jackson et al, 1998), as discussed below, ascorbate concentrations in nucleated cells are typically in the low millimolar range. Whereas ascorbate can act as a pro-oxidant, its relatively high intracellular concentrations, coupled with redundant mechanisms for its regeneration, appear on the whole to protect DNA, protein and lipid from oxidant damage (Carr & Frei, 1999).…”