EFFECT OF ISCHEMIC PRECONDITIONING ON VASCULAR DYSFUNCTION INDUCED BYISCHEMIA AND REPERFUSION IN RAT HINDQUARTERS

Objective: The aim of this study was to examine the effect of ischaemi a on vascular responses to endothelium-dependent and endothelium-indep endent vasodilators and on vasoconstrictor responses. Furthermore, the ability of preconditioning to prevent ischaemia-induced changes in va scular reactivity was examined in the rat hindquarters. Methods: The a bdominal aortae of anaesthetized rats were cannulated for hindquarters perfusion with Krebs bicarbonate solution containing phenylephrine to induce vasoconstrictor tone. Responses of the hindquarters to endothe lium-dependent and endothelium-independent vasodilators were examined. Hindquarters responses to neuronal release of the vasodilator acetylc holine (ACh) induced by peri-aortic nerve stimulation were also examin ed. Results: Ischaemia with 2 h aortic occlusion prior to Krebs perfus ion attenuated vasodilator responses to the neuronal release of ACh [1 0 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 mu g; Delta PP control: -21(3) mmHg, ischaemic: -12(3) mmHg]. Responses to other e ndothelium-dependent vasodilators bradykinin and histamine or the endo thelium-independent vasodilator, sodium nitroprusside, were not impair ed by ischaemia. Similarly vasoconstriction to noradrenaline and serot onin was not affected. Ischaemia preceded by preconditioning with 5 mi n aortic occlusion and 10 min reperfusion prevented impairment of vaso dilatation to nerve stimulation [10 Hz; Delta PP preconditioned: -20(1 ) mmHg], ACh [10 ng; Delta PP preconditioned: -22(1) mmHg] and carbach ol [1.0 mu g; Delta PP preconditioned: -24(3) mmHg] caused by ischaemi a. Conclusions: These data indicate that hindquarters ischaemia causes selective impairment of dilator responses to muscarinic agonists and ischaemic preconditioning prevents that impairment.