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.