The role of the A(2A) adenosine receptor subtype in functional hyperaemia in the hindlimb of anaesthetized cats.
1. The present study was designed to investigate the contribution of the A(2A) adenosine receptor subtype in the functional hyperaemia response during muscle contraction. 2. In cats anaesthetized with sodium pentobarbitone and breathing spontaneously following tracheotomy, the left sciatic and femoral nerves were electrically stimulated at 3 Hz for 20 min to induce muscle contraction, and hindlimb blood flow was measured with a flow probe. The contribution of the A(2A) adenosine receptor subtype was assessed using ZM 241385, a potent and selective A(2A) adenosine receptor antagonist. 3. In a control group, the muscle isometric tension measured in the extensor digitorum longus-tibialis anterior muscle group was 6.64 +/- 0.66 kg (100 g muscle mass)(-1) and hindlimb vascular conductance was 0.22 +/- 0.03 ml mmHg(-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 unaffected (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 contraction. Hindlimb conductance response was reduced by 27.1 +/- 4.8% following the A(2A) selective adenosine receptor antagonist, similar to that observed with the non-selective antagonist 8-phenyltheophylline. 5. These results show that adenosine acting at the A(2A) subtype receptor can contribute up to 30% of the functional hyperaemia response in the hindlimb of anaesthetized cats.
Poucher
S M
SM
Cardiovascular and Metabolism Department, Zeneca Pharmaceuticals, Macclesfield, Cheshire, UK.
D000241:Adenosine / Q000037:antagonists & inhibitors; D000818:Animals; D001158:Arteries / Q000378:metabolism; D002415:Cats; D005740:Gases / Q000097:blood; D006614:Hindlimb / Q000098:blood supply*; D006863:Hydrogen-Ion Concentration; D006940:Hyperemia / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D007537:Isometric Contraction; D008297:Male; D009132:Muscles / Q000503:physiopathology; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
D005740:Gases; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine