The changes in interstitial adenosine concentration in red or white muscle in response to muscle contractions or systemic hypoxia

Abstract

It is well known that red muscles release adenosine during muscle contractions, and the adenosine dilates the resistance vessels, which increases the blood flow to the muscle. Previously, it was reported that the output of adenosine into the venous blood from white muscles did not change during muscle contractions, although studies with an adenosine receptor antagonist indicated that adenosine did contribute to the exercise hyperaemia. This led to the proposal that the change in interstitial adenosine in white muscle is much smaller than that in red muscle, and is restricted to the immediate vicinity of the resistance vessels. In systemic hypoxia, adenosine is also reported to contribute to vasodilation in skeletal muscle, although its relative contribution in red or white muscle is unknown. The present experiments were performed to test directly the changes in interstitial adenosine concentration in red and white muscle during muscle contractions or hypoxia. Experiments were performed in 22 SpragueDawley rats, anaesthetised with sodium pentobarbital (i.p.). The skin overlying the hindlimb muscle was opened, and a microdialysis probe was inserted through a hypodermic needle into the body of the soleus (SL, red) muscle or the extensor digitorum longus (EDL, white) muscle. The probe was perfused at 2 Ìl/min with physiological saline, and the preparation was allowed to equilibrate for 1 hour prior to any sample collection. Supramaximal stimulation at 2 Hz was delivered for 15 min through electrodes placed on the surface of the muscle. Interstitial adenosine concentration increased from 572 B 203 to 1,881 B 624 nM (n = 10; p ! 0.05) in EDL, but did not increase significantly in SL (180 B 39 nM at rest and 210 B 51 nM (n = 9) during contractions). Systemic hypoxia was induced by reducing the inspired oxygen concentration from 20 to 10%: hypoxia significantly decreased interstitial adenosine from 107 B 9 to 83 B 7 nM in EDL (n = 8; p ! 0.5), and from 98 B 10 to 69 B 5 nM in SL (n = 8; p ! 0.005). These data suggest that: (i) the adenosine produced during systemic hypoxia may originate from the vascular endothelium, since it is not distributed throughout the interstitial space; (ii) the interstitial adenosine concentration in white muscle may reach higher levels than that in red muscle since the lower blood flow fails to wash it out. We suggest that the smaller hyperaemia seen in white muscle may result from a lower density of adenosine receptors rather than a lower adenosine production.