In humans, the net effect of acute systemic hypoxia in quiescent skeletal muscle is vasodilation despite reflex increases in muscle sympathetic vasoconstrictor nerve activity. This vasodilation increases tissue perfusion and oxygen delivery to maintain tissue oxygen consumption. Although several mechanisms may be involved, we recently tested the roles of two endothelial-derived substances during conditions of sympathoadrenal blockade to isolate local vascular control mechanisms: nitric oxide (NO) and prostaglandins (PGs). Our findings indicate that (1) NO normally plays a role in regulating vascular tone during hypoxia independent of the PG pathway; (2) PGs do not normally contribute to vascular tone during hypoxia, however do impact vascular tone when NO is inhibited; (3) NO and PGs are not independently obligatory to observe hypoxic vasodilation when assessed as a response from rest to steady-state hypoxia; and (4) combined NO and PG inhibition abolishes hypoxic vasodilation in human skeletal muscle. When the stimulus is exacerbated via combined submaximal rhythmic exercise and systemic hypoxia to cause further red blood cell (RBC) deoxygenation, blood flow is augmented compared with normoxic exercise via local dilator mechanisms to maintain oxygen delivery to the active tissue. Data obtained in a follow-up study indicate that combined NO and PG inhibition during hypoxic exercise blunts the augmented vasodilation and hyperemia compared with control (normoxic) conditions ~50%, however the response is not abolished implicating other local substances are involved. Factors associated with greater RBC deoxygenation such as ATP release and/or nitrite reduction to NO likely play a role in regulating this response.
- Copyright © 2015, Journal of Applied Physiology