Interstitial adenosine but not nitric oxide concentrations are elevated during systemic hypoxia in rat skeletal muscle

Abstract

During systemic hypoxia it is generally accepted that nitric oxide (NO) and adenosine (Ado) contribute to peripheral vasodilatation in skeletal muscle. To examine this, microdialysis fibers were inserted into the gastrocnemius muscle of anesthetized rats (n = 16) and perfused with ringers (control), 60 μM ATP (Ado precursor) or 500 μM AOPCP (5′ectonucleotidase inhibitor) at a rate of 5 μL/min during rest and hypoxia (10.5% O2). During all perfusions and conditions no changes in interstitial NO concentrations were observed. Interstitial Ado levels during ringers perfusion were 0.04±0.01 μM at rest and increased to 0.07±0.01 μM during hypoxia (P<0.05). The perfusion of ATP alone increased (P<0.05) interstitial Ado levels from 0.04±0.01 μM to 0.12±0.02 μM at rest and hypoxia further increased (P<0.05) Ado levels to 0.18±0.02 μM. Perfusion of AOPCP reduced interstitial Ado to undetectable levels throughout the experiment, confirming inhibition of the 5′ectonucleotidase and subsequently Ado production. These data clearly demonstrate that hypoxia and alterations in Ado concentrations do not directly affect NO concentrations. In particular, when Ado production was inhibited, NO did not compensate for the loss of this vasodilator, even during hypoxia. Furthermore, interstitial Ado levels were elevated during hypoxia and appear to play a key role in interstitially mediated vasodilation.Supported by NSERC.