Endothelin‐1 ‐induced reduction of myocardial infarct size by activation of ATP‐sensitive potassium channels in a rabbit model of myocardial ischaemia and reperfusion

Abstract

. This study examined whether endothelin‐1 (ET‐1) reduces infarct size in a rabbit model of acute coronary artery occlusion (60 min) and reperfusion (120 min). In addition, we investigated whether the observed cardioprotective effect of ET‐1 was due to the activation of ATP‐sensitive potassium (KAtp) channels by using two selective antagonists, glibenclamide and sodium 5‐hydroxydecanoate (5‐HD). . In the anaesthetized rabbit, infarct size (expressed as a percentage of the area at risk) after 60 min of coronary artery occlusion followed by 2h of reperfusion was 55 ± 4% (n=ll). ET‐1 (0.3 nmol kg−1), administered as a bolus injection into the left ventricle, had no effect on infarct size (62 ±2, n = 4). A lower dose of ET‐1 (0.03 nmol kg−1) resulted in a significant reduction in infarct size (infarct size 43 ±3%; P<0.05, n= 16). The higher dose (0.3 nmol kg−1), but not the lower dose of ET‐1 caused a significant rise in blood pressure, pressure rate index and hence, myocardial oxygen consumption. . The reduction in infarct size afforded by ET‐1 (0.03 nmol kg−1) was abolished by pretreatment of rabbits with the KATP channel inhibitors, glibenclamide (0.3 mg kg−1) and 5‐HD (5 mg kg−1), (infarct size 59 ±3 and 63 ±4% respectively; n= 4–9). . We propose that ET‐1 reduces infarct size by opening KAtp channels. 1995 British Pharmacological Society