ISCHEMIA-REPERFUSION ENHANCES PHENYLEPHRINE-INDUCED CONTRACTION OF RABBIT AORTA DUE TO IMPAIRMENT OF NEURONAL UPTAKE

We studied the effect of ischaemia and reperfusion on vasoconstrictor and vasodilator mechanisms. Anaesthetized rabbits were subjected to 4- h abdominal aortic occlusion and 1-h reperfusion in vivo. Segments of the abdominal (ischaemic-reperfused) and thoracic (control) aorta were then removed for in vitro studies. Ischaemia/reperfusion had no signi ficant effect on relaxant responses to either acetylcholine (ACh:endot helium-dependent) or sodium nitroprusside (SNP:endotheliumin-dependent ). The sensitivity of the aorta to contraction by phenylephrine was si gnificantly increased in aortic rings with or without endothelium (by 2.2- and 3.7-fold, respectively), but was not different after 4-h isch aemia without reperfusion. In contrast, responses to methoxamine, sero tonin, and U46619 were not affected by ischaemia/reperfusion. Moreover , the relative increase in aortic sensitivity to phenylephrine was pre vented by treatment of control and ischaemic-reperfused aortic rings w ith the neuronal uptake inhibitor cocaine (10(-5) M). These results su ggest that after 4-h ischaemia, reperfusion damages sympathetic neuron al uptake mechanisms in rabbit aorta. As a result, phenylephrine, an a gonist normally susceptible to neuronal uptake, may exert more potent contractile effects. Endothelium-dependent and endothelium-independent relaxant mechanisms in the aorta appear to be resistant to acute isch aemia and reperfusion.