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

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 mu g/min), or diltiazem (3.6-14.4 mu g/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/100 ml, 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/100 ml at the highest dose, P=0.05). Increasing blood flow induces oxidative stress through a NO- and endothelium-independent mechanism. (C) 2010 Elsevier Inc. All rights reserved.