Exercise attenuates alpha-adrenergic-receptor responsiveness in skeletal muscle vasculature.

Attenuation of sympathetic vasoconstriction (sympatholysis) in working muscles during dynamic exercise is controversial. A potential mechanism is a reduction in alpha-adrenergic-receptor responsiveness. The purpose of this study was to examine alpha(1)- and alpha(2)-adrenergic-receptor-mediated vasoconstriction in resting and exercising skeletal muscle using intra-arterial infusions of selective agonists. Thirteen 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. Intra-arterial infusions of phenylephrine elicited reductions in vascular conductance of 76 +/- 4, 71 +/- 5, and 31 +/- 2% at rest, 3 miles/h, and 6 miles/h and 10% grade, respectively. Intra-arterial clonidine reduced vascular conductance by 81 +/- 5, 49 +/- 4, and 14 +/- 2%, respectively. The response to intra-arterial infusion of clonidine was unaffected by surgical sympathetic denervation. Agonist infusion did not affect either systemic blood pressure, heart rate, or blood flow in the contralateral iliac artery. 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. These results suggest that the mechanism of exercise sympatholysis may involve reductions in postsynaptic alpha-adrenergic-receptor responsiveness.