POSTISCHEMIC VASODILATION IN HUMAN FOREARM IS DEPENDENT ON ENDOTHELIUM-DERIVED NITRIC-OXIDE

Although endothelium-derived nitric oxide contributes to basal vascula r tone, little is known about its role in regulating blood flow during changes in metabolic supply and demand. We examined the contribution of endothelium-derived nitric oxide to reactive hyperemia in the forea rm of 20 normal subjects (12 women, 8 men) aged 27 +/- 4 yr (means +/- SD), using the nitric oxide synthase inhibitor, N-G-monomethyl-L-argi nine (L-NMMA). Forearm ischemia was induced by suprasystolic blood pre ssure cuff inflation for 5 min, and the subsequent hyperemic flow was recorded for 5 min using venous occlusion strain-gauge plethysmography . The efficacy of nitric oxide blockade was tested by comparing the do se-response relationship to the endothelium-dependent agonist, acetylc holine (3, 10, and 30 mg/min), before and after intra-arterial infusio n of up to 2,000 mg/min of L-NMMA. L-NMMA produced a significant downw ard and rightward shift in the dose-response relationship to acetylcho line and a 39% reduction in response to the maximum dose (P < 0.001). In the presence of L-NMMA, peak hyperemic flow was reduced 16% (26.5 /- 2.1 to 22.3 +/- 1.5 ml . min(-1) . 100 ml of forearm(-1), P < 0.03) , and the minimum forearm vascular resistance was increased 22.8% (3.5 +/- 0.3 to 4.3 +/- 0.4 mmHg . ml(-1) . min . 100 ml, P < 0.02). Total hyperemia, calculated from the area under the flow vs. time curve, at 1 and 5 min after cuff release was 17 and 23% less, respectively (13. 6 +/- 1.2 vs. 11.3 +/- 1.1 and 31.8 +/- 2.7 vs. 24.6 +/- 1.8 ml/100 ml , P < 0.002), following L-NMMA. These data suggest that endothelium-de rived nitric oxide plays a role in both reactive hyperemia and in the maintenance of the hyperemic response following ischemia in the forear m.