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.