Journal of Applied Physiology AJP: Heart and Circulatory Physiology
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J Appl Physiol 97: 417-423, 2004. First published March 12, 2004; doi:10.1152/japplphysiol.01181.2003
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HIGHLIGHTED TOPICS
Skeletal and cardiac muscle blood flow

Role of nitric oxide in exercise sympatholysis

John B. Buckwalter, Jessica C. Taylor, Jason J. Hamann, and Philip S. Clifford

Departments of Anesthesiology and Physiology, Medical College of Wisconsin and Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295

Submitted 4 November 2003 ; accepted in final form 10 March 2004

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 {alpha}-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 {alpha}1-adrenergic agonist (phenylephrine) or the selective {alpha}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 NG-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. {alpha}1-Adrenergic-receptor responsiveness was attenuated during heavy exercise. In contrast, {alpha}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 {alpha}1-adrenergic-receptor responsiveness, the attenuation of {alpha}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.

blood flow; autonomic nervous system; dogs; vasoconstriction



Address for reprint requests and other correspondence: J. B. Buckwalter, Anesthesia Research 151, VA Medical Center, Milwaukee, WI 53295 (E-mail: jbuckwal{at}mcw.edu).




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