CONTRIBUTION OF NITRIC-OXIDE TO REACTIVE HYPEREMIA - IMPACT OF ENDOTHELIAL DYSFUNCTION

Our objectives were to (1) test the hypothesis that nitric oxide (NO) contributes to peak reactive hyperemia (RH) in the human peripheral va sculature, (2) examine the impact of atherosclerosis and its risk fact ors on RH, and (3) investigate whether L-arginine will improve RH in p atients with endothelial dysfunction. The endothelium contributes to s hear stress-mediated vasomotion by releasing a variety of dilating fac tors, including NO, but the contribution of NO to peak RH in patients with and without endothelial dysfunction is unknown. Endothelium-depen dent and endothelium-independent function was assessed with intrafemor al arterial acetylcholine (ACh) and sodium nitroprusside. RH was produ ced by occlusion of blood flow to the leg for 3 minutes. The study was repeated after N-G-monomethyl-L-arginine (L-NMMA) in 44 subjects and L-arginine in 9 patients with atherosclerosis. There were 15 normal co ntrol subjects without risk factors for atherosclerosis and 29 patient s with risk factors or angiographic atherosclerosis. Microvascular vas odilation in response to ACh, but not to sodium nitroprusside, was low er in the patients with risk factors or atherosclerosis compared with normal control subjects, P=0.048, and the inhibition of ACh-induced mi crovascular dilation by L-NMMA was also greater in normal control subj ects (P=0.045). Similarly, RH, including the peak response, was inhibi ted by L-NMMA in normal control subjects (P=0.0011) but not in patient s with risk factors or atherosclerosis, suggesting that the contributi on of NO to both ACh-induced dilation and RH was diminished in patient s with risk factors or atherosclerosis. L-Arginine did not affect vaso dilation in response to ACh, sodium nitroprusside, or RH. We concluded that (1) NO contributes to all phases of RH in the normal human perip heral vasculature, (2) patients with atherosclerosis or its risks have abnormal NO bioactivity in response to pharmacological and physiologi cal stimulation, and (3) L-arginine does not improve RH in atheroscler osis. Reduced physiological vasodilation in atherosclerosis may contri bute to or exacerbate hypertension and ischemia.