Adenosine and muscle vasodilatation in acute systemic hypoxia

Adenosine is released by skeletal and cardiac muscles when their metabolism increases: it serves to couple O-2 supply with O-2 demand by causing vasodilatation. This review argues that adenosine plays a similar role in skeletal muscle in systemic hypoxia. It accounts for approximate to 50% of the increase in muscle vascular conductance and, within muscle, it causes dilatation of individual arterioles, thus maximizing the distribution of O-2 and allowing O-2 consumption to remain constant when O-2 delivery is reduced. In vivo and in vitro studies have indicated that adenosine can induce dilatation in several different ways. This review argues that during systemic hypoxia, adenosine is predominantly released from the endothelium and acts on endothelial A(1) receptors to produce dilatation in a nitric oxide (NO)-dependent manner. A(1) receptor stimulation increases the synthesis of NO by a process initiated by opening of ATP-sensitive K+ (K-ATP) channels. Moreover, recent findings suggest that prostaglandins also make a major contribution to the hypoxia-induced dilatation, but that the dilator pathways for adenosine, NO and prostaglandins are interdependent. In addition, adenosine released from the skeletal muscle fibres contributes indirectly to the dilatation by stimulating A(1) and A(2) receptors on the muscle fibres, opening K-ATP channels and allowing efflux of K+, which is a vasodilator. Finally, by acting on endothelial A(1) receptors, adenosine attenuates the vasoconstrictor effects of constant or bursting patterns of sympathetic activity. This limits the extent to which the sympathetic nervous system can reduce O-2 delivery to muscle when it is already compromized by systemic hypoxia.