915-82 Contribution of Nitric Oxide to Post-Ischemic Hyperemia: The Consequences of Endothelial Dysfunction

Abstract

Post-ischemic vasodilation during reactive hyperemia is believed to be primarily due to accumulation of ischemic metabolites. To investigate the contribution of nitric oxide (NO) release from vascular endothelium to reactive hyperemia in humans, we studied the effect of inhibition of NO synthesis using L-N G monomethyl arginine (L-NMMA) in 40 pts, 22 with, and 18 without coronary artery disease. Endothelium-dependent and independent dilation, before and after L-NMMA, was measured in the femoral circulation with intra-arterial acetylcholine (ACH) and sodium nitroprusside (SNP), respectively. Three and 5 minutes periods of ischemia were produced by cuff inflation over the thigh and peak hyperemic responses were measured. Femoral vascular resistance was derived from continuous Doppler flow velocity and blood pressure measurements. %Increase in Vascular Resistance with L-NMMA Baseline ACH SNP 3’lschemia 5’lschemia 40 ± 24 ** 57 ± 51 ** 10 ± 4 24 ± 29 ** 17 ± 19 * mean ± SO * p < 0.01 ** p < 0.001 L-NMMA produced a significant increase in vascular resistance at rest, after ACH, and after 3 and 5 minute periods of ischemia and hyperemia, but did not affect endothelium-independent dilation with SNP. Pts with greater inhibition of ACH-induced dilation with L-NMMA also had a greater inhibition of reactive hyperemia with L-NMMA (r = 0.47, P < 0.001). 1) NO release contributes to microvascular vasodilation in response to ischemia, and 2) endothelial dysfunction resulting in reduced release of NO in response to ACH correlates with diminished vasodilatory response to reactive hyperemia. These findings suggest that the contribution of NO to vasodilation in response to metabolic stress is attenuated in pts with endothelial dysfunction and imply that endothelial dysfunction in the coronary vasculature may, by limiting vasodilation during stress, also accentuate myocardial ischemia.