Sympathetic restraint of muscle blood flow during hypoxic exercise

Control of exercising muscle blood flow is a balance between local vasodilatory factors and the increase in global sympathetic vasoconstrictor outflow. Hypoxia has been shown to potentiate the muscle sympathetic nerve response to exercise, potentially limiting the increase in muscle blood flow. Accordingly, we investigated sympathetic restraint to exercising muscle during whole body exercise in hypoxia. Six dogs chronically instrumented with ascending aortic and hindlimb flow probes and a terminal aortic catheter were studied at rest and mild [2.5 miles/h (mph), 5% grade] and moderate (4.0 mph, 10% grade) exercise while breathing room air or hypoxia (Pa(O(2)) approximately 45 mmHg) in the intact control condition and following systemic alpha-adrenergic blockade (phentolamine). Hypoxia caused an increase in cardiac output (CO), hindlimb flow (Flow(L)), and blood pressure (BP), while total (Cond(T)) and hindlimb conductance (Cond(L)) were unchanged at rest and mild exercise but increased with moderate exercise. During both mild and moderate exercise, alpha-blockade in normoxia resulted in significant vasodilation as evidenced by increases in CO (10%), Flow(L) (17%), Cond(T) (33%), Cond(L) (43%), and a decrease in BP (-18%), with the increase in Cond(L) greater than the increase in Cond(T) during mild exercise. Compared with the normoxic response, alpha-blockade in hypoxia during exercise resulted in a significantly greater increase in Cond(T) (59%) and Cond(L) (74%) and a correspondingly greater decrease in BP (-34%) from baseline. These findings indicate that there is considerable hypoxia-induced sympathetic restraint of muscle blood flow during both mild and moderate exercise, which helps to maintain arterial blood pressure in hypoxia.