Prostaglandins do not contribute to the nitric oxide-mediated compensatory vasodilation in hypoperfused exercising muscle

Casey DP, Joyner MJ. Prostaglandins do not contribute to the nitric oxide-mediated compensatory vasodilation in hypoperfused exercising muscle. Am J Physiol Heart Circ Physiol 301: H261-H268, 2011. First published May 2, 2011; doi:10.1152/ajpheart.00222.2011.-We tested the hypothesis that 1) prostaglandins (PGs) contribute to compensatory vasodilation in contracting human forearm subjected to acute hypoperfusion, and 2) the combined inhibition of PGs and nitric oxide would attenuate the compensatory vasodilation more than PG inhibition alone. In separate protocols, subjects performed forearm exercise (20% of maximum) during hypoperfusion evoked by intra-arterial balloon inflation. Each trial included baseline, exercise before inflation, exercise with inflation, and exercise after deflation. Forearm blood flow (FBF; ultrasound) and local (brachial artery) and systemic arterial pressure [mean arterial pressure (MAP); Finometer] were measured. In protocol 1 (n = 8), exercise was repeated during cyclooxygenase (COX) inhibition (Ketorolac) alone and during Ketorolac-NOS inhibition [N(G)-monomethyl-L-arginine (L-NMMA)]. In protocol 2 (n = 8), exercise was repeated during L-NMMA alone and during L-NMMA-Ketorolac. Forearm vascular conductance (FVC; ml.min(-1).100 mmHg(-1)) was calculated from FBF (ml/min) and local MAP (mmHg). The percent recovery in FVC during inflation was calculated as (steady-state inflation + exercise value - nadir)/[steady-state exercise (control) value - nadir] x 100. In protocol 1, COX inhibition alone did not reduce the %FVC recovery compared with the control (no drug) trial (92 +/- 11 vs. 100 +/- 10%, P = 0.83). However, combined COX-nitric oxide synthase (NOS) inhibition caused a substantial reduction in %FVC recovery (54 +/- 8%, P < 0.05 vs. Ketorolac alone). In protocol 2, the percent recovery in FVC was attenuated with NOS inhibition alone (69 +/- 9 vs. 107 +/- 10%, P < 0.01) but not attenuated further during combined NOS-COX inhibition (62 +/- 10%, P = 0.74 vs. L-NMMA alone). Our data indicate that PGs are not obligatory to the compensatory dilation observed during forearm exercise with hypoperfusion.