HIGHLIGHTED TOPIC Skeletal and Cardiac Muscle Blood Flow Role of nitric oxide in exercise sympatholysis

Buckwalter, John B., Jessica C. Taylor, Jason J. Hamann, and Philip S. Clifford. Role of nitric oxide in exercise sympatholysis. J Appl Physiol 97: 417–423, 2004. First published March 12, 2004; 10.1152/japplphysiol.01181.2003.—The production of nitric oxide is the putative mechanism for the attenuation of sympathetic vasoconstriction (sympatholysis) in working muscles during exercise. We hypothesized that nitric oxide synthase blockade would eliminate the reduction in -adrenergic-receptor responsiveness in exercising skeletal muscle. Ten mongrel dogs were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. The selective 1-adrenergic agonist (phenylephrine) or the selective 2-adrenergic agonist (clonidine) was infused as a bolus into the femoral artery catheter at rest and during mild and heavy exercise. Before nitric oxide synthase inhibition with N-nitro-L-arginine methyl ester (L-NAME), intra-arterial infusions of phenylephrine elicited reductions in vascular conductance of 91 3, 80 5, and 75 6% (means SE) at rest, 3 miles/h, and 6 miles/h and 10% grade, respectively. Intra-arterial clonidine reduced vascular conductance by 65 6, 39 4, and 30 3%. After L-NAME, intra-arterial infusions of phenylephrine elicited reductions in vascular conductance of 85 5, 85 5, and 84 5%, whereas clonidine reduced vascular conductance by 67 5, 45 3, and 35 3%, at rest, 3 miles/h, and 6 miles/h and 10% grade. 1-Adrenergic-receptor responsiveness was attenuated during heavy exercise. In contrast, 2-adrenergic-receptor responsiveness was attenuated even at a mild exercise intensity. Whereas the inhibition of nitric oxide production eliminated the exercise-induced attenuation of 1-adrenergic-receptor responsiveness, the attenuation of 2-adrenergic-receptor responsiveness was unaffected. These results suggest that the mechanism of exercise sympatholysis is not entirely mediated by the production of nitric oxide.