THE ROLE OF THE A(2A) ADENOSINE RECEPTOR SUBTYPE IN FUNCTIONAL HYPEREMIA IN THE HINDLIMB OF ANESTHETIZED CATS

1. The present study was designed to investigate the contribution of t he A(2A) adenosine receptor subtype in the functional hyperaemia respo nse during muscle contraction. 2. In cats anaesthetized with sodium pe ntobarbitone and breathing spontaneously following tracheotomy, the le ft sciatic and femoral nerves were electrically stimulated at 3 Hz for 20 min to induce muscle contraction, and hindlimb blood flow was meas ured with a flow probe. The contribution of the A(2A) adenosine recept or subtype was assessed using ZM 241385, a potent and selective A(2A) adenosine receptor antagonist. 3. In a control group, the muscle isome tric tension measured in tile extensor digitorum longus-tibialis anter ior muscle group was 6.64 +/- 0.66 kg (100 g muscle mass)(-1) and hind limb vascular conductance was 0.22 +/- 0.03 ml mmg(-1) (kg body mass)( -1) at 20 min of contraction. Administration of vehicle did not affect these parameters upon a second contraction period: 6.31 +/- 0.61 kg ( 100 g muscle mass)(-1) and 0.23 +/- 0.03 ml mmHg(-1) (kg body mass)(-1 ), respectively. Total hindlimb conductance during contraction was una ffected (5.5 +/- 3.7% decrease). 4. ZM 241385 (1.0 mg kg(-1)) did not alter the amount of force produced by the muscle at 20 min of contract ion. Hindlimb conductance response was reduced by 27.1 +/- 4.8% follow ing the A(2A) selective adenosine receptor antagonist, similar to that observed with the non-selective antagonist 8-phenyltheophylline 5. Th ese results show that adenosine acting at the A(2A) subtype receptor c an contribute up to 30% of the functional hyperaemia response in the h indlimb of anaesthetized cats.