Increased blood flow induces oxidative stress through an endothelium- and nitric oxide-independent mechanism.

Fong P, Stafforini DM, Brown NJ, Pretorius M
Free Radic Biol Med. 2010 49 (2): 301-5

PMID: 20423727 · PMCID: PMC2916026 · DOI:10.1016/j.freeradbiomed.2010.04.023

Bradykinin, a potent vasodilator, stimulates the formation of reactive oxygen species and F(2)-isoprostanes in vitro. The effect of bradykinin on oxidative stress in humans is not known. This study tested the hypothesis that bradykinin induces oxidative stress through a nitric oxide (NO)-dependent mechanism in the human vasculature. We measured forearm blood flow (FBF) and net F(2)-isoprostane release in response to intraarterial bradykinin (50-200 ng/min), nitroprusside (1.6-6.4 microg/min), or diltiazem (3.6-14.4 microg/min) in the absence and presence of the NO synthase inhibitor N(omega)-monomethyl-L-arginine (L-NMMA) in normotensive and hypertensive subjects pretreated with aspirin. L-NMMA significantly decreased basal FBF and basal net F(2)-isoprostane release (from 28.7+/-5.2 to 13.4+/-3.5 pg/min/100ml, P=0.01) in all subjects. Bradykinin caused a significant increase in FBF and net F(2)-isoprostane release in both normotensive and hypertensive subjects. During NO synthase inhibition, bradykinin significantly increased net F(2)-isoprostane release in both groups (P=0.001) and there was no effect of L-NMMA on bradykinin-stimulated F(2)-isoprostane release (P=0.46). Nitroprusside also significantly increased net F(2)-isoprostane release in hypertensive subjects (P=0.01) and this response was not affected by L-NMMA (P=0.50). Diltiazem increased FBF as well as net F(2)-isoprostane release (from 44.5+/-12.5 to 61.2+/-14.7 pg/min/100ml at the highest dose, P=0.05). Increasing blood flow induces oxidative stress through a NO- and endothelium-independent mechanism.

Copyright 2010 Elsevier Inc. All rights reserved.

MeSH Terms (18)

Adult Bradykinin Calcium Channel Blockers Diltiazem Endothelium, Vascular F2-Isoprostanes Female Humans Hypertension Male Middle Aged Nitric Oxide Nitric Oxide Donors Nitroprusside omega-N-Methylarginine Oxidative Stress Regional Blood Flow Vasodilator Agents

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