Relative contribution of vasodilator prostanoids and NO to metabolic vasodilation in the human forearm

Although many factors are thought to contribute to the regulation of metabo lic vasodilation in skeletal muscle vasculature, recent interest has focuse d on the role of the endothelium. We examined the relative roles of nitric oxide (NO) and of vasodilator prostanoids in the control of metabolically i nduced functional hyperemia in the forearm of humans. In 43 healthy volunte ers [24 +/- 5 (SD) yr] we assessed resting and functional hyperemic blood f low (FHBF) in response to 2 min of isotonic forearm exercise before and aft er inhibition of NO and/or vasodilator prostanoid production with intra-art erial N-G-monomethyl-L-arginine (L-NMMA, 2 mg/min) and aspirin (ASA, 3 mg/m in), respectively. Blood flow was measured using venous occlusion plethysmo graphy. L-NMMA and ASA decreased resting forearm blood flow by 42% (P < 0.0 001) and 23% (P < 0.0001), respectively, whereas infusion of ASA followed b y L-NMMA reduced flow by a further 24% (P < 0.05). L-NMMA reduced peak FHBF by 18% [from 13.9 +/- 1.0 to 11.4 +/- 1.1 (SE) ml.100 ml forearm(-1).min(- 1), P = 0.003] and the volume "repaid" after 1 and 5 min by 25% (8.9 +/- 0. 7 vs. 6.7 +/- 0.7 ml/100 ml, P < 0.0001) and 37% (26.6 +/- 1.8 vs. 16.8 +/- 1.6 ml/100 mi, P < 0.0001). ASA similarly reduced peak FHBF by 19% (from 1 4.5 +/- 1.1 to 11.8 +/- 0.9 . 100 ml forearm(-1).min(-1), P < 0.001) and th e volume repaid after 1 and 5 min by 14% (7.5 +/- 0.6 vs. 6.4 +/- 0.6 ml/10 0 ml, P = 0.0001) and 20% (21.2 +/- 1.5 vs. 16.9 +/- 1.5 ml/100 mi, P < 0.0 001), respectively. The coinfusion of ASA and L-NMMA did not decrease FHBF to a greater extent than either agent alone. These data suggest that endoth elium-derived NO and vasodilator prostanoids contribute to resting blood fl ow and metabolic vasodilation in skeletal muscle vasculature in healthy hum ans. Although these vasodilator mechanisms operate in parallel in exercise- induced hyperemia, they appear not to be additive. Other mechanisms must al so be operative in metabolic vasodilation.