To elucidate the mechanism responsible for the ischemia-induced norepinephrine (NE) efflux from cardiac sympathetic nerve endings, we applied dialysis technique to the heart of anesthetized cats and monitored myocardial interstitial NE levels during 120 min-coronary occlusion and after reperfusion. We locally administered neuronal blockades to the ischemic region through a dialysis probe and compared the ischemia-induced increase of interstitial NE in the presence and absence of these blockades. 1) Coronary occlusion markedly increased interstitial NE levels in the ischemic region, but not in the non-ischemic region. After reperfusion, NE levels decreased in the ischemic region, and there was no significant difference in tyramine-induced NE efflux between the ischemic and non-ischemic regions. 2) ω-Conotoxin GVIA (N-type Ca2+ channel antagonist) suppressed the increase in interstitial NE levels within 20 min of occlusion, but did not suppress NE increase after 20 min of occlusion. 3) Desipramine (inhibitor of uptake1 carrier) suppressed the increase in interstitial NE levels at 20-60 min of occlusion, but NE levels gradually increased and reached the same level as those in the vehicle group at 120 min of occlusion. 4) Addition of TMB-8 (intracellular Ca2+ release inhibitor) to desipramine further suppressed the increase in interstitial NE levels during the 60-120 min of occlusion. Our results suggest three different mechanisms of ischemia-induced NE efflux to operate subsequently during the course of myocardial ischemia. [Jpn J Physiol 54 Suppl:S60 (2004)]
