Ischaemic skeletal muscle hyperaemia in the anaesthetized cat: no contribution of A2A adenosine receptors.
1. The present study investigated the contribution of the A2A adenosine receptor subtype to the functional hyperaemia response evoked by muscle contraction in anaesthetized cats when muscle blood flow was limited. 2. Application of a stenosis reduced the hindlimb blood flow at rest from 9.67 +/- 1.80 to 5.53 +/- 0.91 ml min(-1) (kg body mass)(-1) and during muscle contraction from 36.80 +/- 2.55 to 11.11 +/- 1.19 ml min(-1) (kg body mass)(-1) (P < 0.001). The force produced by the extensor digitorum longus and tibialis anterior (EDL-TA) muscle groups was also reduced, from 9.66 +/- 0.56 to 4.10 +/- 0.4 N (kg muscle mass)(-1) (P < 0.01). 3. The selective A2A adenosine receptor antagonist ZM241385 (3 mg kg(-1), I.V.) had no effect upon the hindlimb vascular conductance or muscle contraction responses in the presence of the flow-limiting stenosis. 4. In contrast, in the absence of the flow restriction the vascular conductance response was reduced by 27.5 +/- 5.0% (P < 0.05), whilst the isometric force produced by the EDL-TA muscle group was unaffected (pre- vs. post-contraction, 5.8 +/- 0.8 vs. 4.6 +/- 1.0 N (kg muscle mass)(-1) contraction). Oxygen consumption by the contracting hindlimb muscles was maintained (1.71 +/- 0.25 vs. 1.69 +/- 0.26 ml min(-1) (kg body mass)(-1)) by an increase in the oxygen extraction (51.9 +/- 4.9 vs. 66.2 +/- 6.1%; P< 0.01). 5. These results confirm previous data showing that adenosine, acting at the A2A receptor subtype, can contribute up to 30% of the functional hyperaemia response in the hindlimb of anaesthetized cats under free flow conditions. However, when blood flow is limited by a stenosis, antagonism of the A2A adenosine receptor does not affect functional hyperaemia.
Poucher
S M
SM
Cardiovascular & Musculoskeletal Research Department, ZENECA Pharmaceuticals, Macclesfield, Cheshire, UK. simon.poucher@gbapr.zeneca.com
D000768:Anesthesia, General; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004558:Electric Stimulation; D005267:Femoral Nerve / Q000502:physiology / Q000503:physiopathology; D006614:Hindlimb / Q000098:blood supply; D006940:Hyperemia; D007511:Ischemia / Q000503:physiopathology*; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000502:physiology / Q000503:physiopathology*; D010101:Oxygen Consumption / Q000187:drug effects; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D012584:Sciatic Nerve / Q000502:physiology / Q000503:physiopathology; D014227:Triazines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*
D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385