Effect of ischaemic preconditioning on vascular dysfunction induced by ischaemia and reperfusion in rat hindquarters.
OBJECTIVE
The aim of this study was to examine the effect of ischaemia on vascular responses to endothelium-dependent and endothelium-independent vasodilators and on vasoconstrictor responses. Furthermore, the ability of preconditioning to prevent ischaemia-induced changes in vascular reactivity was examined in the rat hindquarters.


METHODS
The abdominal aortae of anaesthetized rats were cannulated for hindquarters perfusion with Krebs bicarbonate solution containing phenylephrine to induce vasoconstrictor tone. Responses of the hindquarters to endothelium-dependent and endothelium-independent vasodilators were examined. Hindquarters responses to neuronal release of the vasodilator acetylcholine (ACh) induced by peri-aortic nerve stimulation were also examined.


RESULTS
Ischaemia with 2 h aortic occlusion prior to Krebs perfusion attenuated vasodilator responses to the neuronal release of ACh [10 Hz; decrease in perfusion pressure (delta PP) control: -18(s.e.m. 3) mmHg, Ischaemic: -13(3) mmHg], exogenous ACh [10 ng; delta PP control: -22(2) mmHg, ischaemic: -17(2) mmHg] and carbachol [1.0 micrograms; delta PP control: -21(3) mmHg, ischaemic: -12(3) mmHg]. Responses to other endothelium-dependent vasodilators bradykinin and histamine or the endothelium-independent vasodilator, sodium nitroprusside, were not impaired by ischaemia. Similarly vasoconstriction to noradrenaline and serotonin was not affected. Ischaemia preceded by preconditioning with 5 min aortic occlusion and 10 min reperfusion prevented impairment of vasodilatation to nerve stimulation [1.0 micrograms; delta PP preconditioned: -24 (3) preconditioned: -20(1) mmHg], ACh [10 ng; delta PP preconditioned: -22(1) mmHG] and carbachol [1.0 micrograms; delta PP preconditioned: -24(3) mmHG]caused by ischaemia.


CONCLUSIONS
These data indicate that hindquarters ischaemia causes selective impairment of dilator responses to muscarinic agonists and ischaemic preconditioning prevents that impairment.
Loke
K E
KE
Department of Pharmacology, University of Melbourne, Parkville, Victoria Australia.
Woodman
O L
OL
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006614:Hindlimb; D007511:Ischemia / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000098:blood supply*; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000503:physiopathology*
D018721:Muscarinic Agonists; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D002217:Carbachol; D000109:Acetylcholine