NOS inhibition blunts and delays the compensatory dilation in hypoperfused contracting human muscles.

We previously demonstrated that skeletal muscle blood flow is restored in the exercising forearm during experimental hypoperfusion via local dilator and/or myogenic mechanisms. This study examined the role of nitric oxide (NO) in the restoration of blood flow to the active muscles during hypoperfusion. Eleven healthy subjects (10 men/1 woman; 25 +/- 1 yr of age) performed rhythmic forearm exercise (10% and 20% of maximum) while hypoperfusion was evoked by balloon inflation in the brachial artery above the elbow. Each trial included baseline, exercise, exercise with inflation, and exercise after deflation (3 min each). Forearm blood flow (FBF; ultrasound) and local (brachial artery catheter pressure, BAP) and systemic arterial pressure [mean arterial pressure (MAP); Finometer] were measured. The exercise bouts were repeated during N(G)-monomethyl-L-arginine (L-NMMA) infusion (NO synthase inhibition). Forearm vascular conductance (FVC; ml x min(-1) x 100 mmHg(-1)) was calculated from BF (ml/min) and BAP (mmHg). FBF and FVC fell acutely with balloon inflation during all trials (P < 0.01). Recovery of FBF and FVC [(inflation - nadir)/(steady-state exercise - nadir)] with L-NMMA administration was reduced during 20% exercise (FBF = 77 +/- 7% vs. 88 +/- 8%; FVC = 71 +/- 8% vs. 90 +/- 9%; P < 0.01) but not 10% exercise (FBF = 83 +/- 4% vs. 81 +/- 5%, P = 0.37; FVC = 75 +/- 10% vs. 76 +/- 7%; P = 0.44) compared with the respective control trial. The time to steady-state vasodilator response was substantially longer during the l-NMMA trials (10% = 74 +/- 4 s vs. 61 +/- 6 s; 20% = 53 +/- 4 s vs. 41 +/- 4 s; P < 0.05). Thus the magnitude and timing of the NO contribution to compensatory dilation during forearm exercise with hypoperfusion was dependent on exercise intensity. These observations suggest that NO is released by contracting muscles or that a portion of the dilation caused by ischemic metabolites is NO dependent.