ENDOTHELIAL MODULATION OF NEURAL SYMPATHETIC VASCULAR TONE IN CANINE SKELETAL-MUSCLE

The effect of nitric oxide synthase (NOS) inhibition and endothelin-A (ETA)receptor blockade on neural sympathetic control of vascular tone in the gastrocnemius muscle was examined in anesthetized dogs under co nditions of constant flow. Muscle perfusion pressure (MPP) was measure d before and after NOS inhibition (N-omega-nitro-L-arginine methyl est er; L-NAME) and ETA-receptor blockade [cyclo-(D-Trp-d-Asp-Pro-D-Val-Le u); BQ-123]. Zero and maximum sympathetic nerve activities were achiev ed by sciatic nerve cold block and stimulation, respectively. In group 1 (n = 6), MPP was measured 1) before nerve cold block, 2) during ner ve cold block, and 3) during nerve stimulation. Measurements under the se conditions were repeated after L-NAME and then BQ-123. The same pro tocol was followed in group 2 (n = 6) except that the order of L-NAME and BQ-123 was reversed. MPP and muscle vascular resistance (MVR) incr eased after L-NAME and then decreased to control values after BQ-123. MVR decreased after BQ-123 alone and, with the addition of L-NAME, inc reased to a level not different from that observed during the control period. MVR fell during nerve cold block. This response was not affect ed by administration of L-NAME followed by BQ-123, but it was attenuat ed by administration of BQ-123 before L-NAME. The constrictor response during sympathetic nerve stimulation was enhanced by L-NAME; no furth er effect was observed with BQ-123, nor was the response affected when BQ-123 was given first. These findings indicate that endothelin contr ibutes to I)basal vascular tone in skeletal muscle and 2) the increase in skeletal muscle vascular resistance after NOS inhibition. Finally, nitric oxide ''buffers' the degree of constriction in skeletal muscle vasculature during maximal sympathetic stimulation.