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

British Journal of Pharmacology
E J HideC Thiemermann

Abstract

1. 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). 2. In the anaesthetized rabbit, infarct size (expressed as a percentage of the area at risk) after 60 min of coronary artery occlusion followed by 2 h of reperfusion was 55 +/- 4% (n = 11). 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. 3. 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...Continue Reading

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Citations

Sep 25, 2001·European Journal of Pharmacology·I SharifC L Wainwright
Jan 1, 1996·Pharmacology & Therapeutics·G A Gray, D J Webb
Sep 18, 1999·Free Radical Biology & Medicine·M C McDonaldC Thiemermann
May 9, 2009·British Journal of Pharmacology·S K WalshC L Wainwright
Feb 7, 2006·Pharmacology & Therapeutics·Friedrich BrunnerAdelino F Leite-Moreira
Aug 7, 2012·Journal of Pharmacological Sciences·Mamoru OhkitaYasuo Matsumura
Jun 17, 2003·Journal of Cardiovascular Pharmacology and Therapeutics·Manjeet Singh, Harjot K Saini
Mar 3, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Hans Erik BøtkerNichlas Riise Jespersen
Oct 16, 1999·Circulation Research·A BaronA J Baertschi
Apr 3, 2014·Physiological Reviews·Ildiko Szabo, Mario Zoratti

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