Role of nitric oxide in exercise sympatholysis.
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 N(G)-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.
Buckwalter
John B
JB
Department of Anesthesiology, Medical College of Wisconsin and Veterans Affairs Medical Center, Milwaukee, WI 53295, USA. jbuckwal@mcw.edu
Taylor
Jessica C
JC
Hamann
Jason J
JJ
Clifford
Philip S
PS
D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply / Q000294:innervation / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D010656:Phenylephrine / Q000494:pharmacology; D005082:Physical Exertion / Q000502:physiology*; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology; D012146:Rest / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D010656:Phenylephrine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D003000:Clonidine; D019331:NG-Nitroarginine Methyl Ester