Involvement of endothelin-1 in acute ischaemic arrhythmias in cats and rats.
This study aims to investigate the role of endothelin-1 (ET-1) in the genesis of acute ischaemic arrhythmias. In anaesthetized cats and rats receiving continuous monitor of electrocardiogram and arterial blood pressure, the ischaemic arrhythmias during 60-min myocardial ischaemia elicited by the occlusion of the left anterior descending coronary artery (LAD) were analysed. To prevent the putative arrhythmic effects of endogenous ET-1, ET(A) receptor antagonist BQ610 (1.5-6.0 nmol/kg) was intracoronary injected just before LAD occlusion in cats, and preproET-1 mRNA antisense oligodeoxynucleotide (AS-ODN; 30-90 nmol/kg) was intravenously injected 2 h before LAD occlusion in rats. The results showed that BQ610 dose-dependently decreased the incidences of ventricular tachycardia (VT) and ventricular fibrillation (VF), and the numbers of ventricular ectopic beats (VEBs). At the dose of 6.0 nmol/kg, the incidence of VT decreased significantly from 33.3% in normal saline (NS) control group to zero (P<0.01), and total VEBs decreased significantly from 831+/-162 to 158+/-51 (P<0.05). In rats receiving ET-1 AS-ODN, plasma ET-1 decreased significantly after 2 h, and remained stable at 30 min of LAD occlusion. However, in rats receiving the control, NS or sense ODN, plasma ET-1 remained unchanged after administration, but increased significantly during LAD occlusion. The ischaemic arrhythmias were dose-dependently suppressed in the presence of ET-1 AS-ODN. At the dose of 90 nmol/kg, the incidence of VT decreased significantly from 100% in both the control groups to 30%. The numbers of single VEBs, consecutive VEBs, VT and total VEBs were also significantly decreased, from 60+/-15 in NS group to 19+/-12, 11+/-3 to 2+/-2, 155+/-41 to 11+/-11, and 239+/-49 to 35+/-25 respectively. In the present cat and rat models of coronary artery occlusion, antagonism of either ET(A) receptors or endogenous ET-1 synthesis prevented the ischaemic arrhythmias, indicating that ET-1 is possibly an important promotive factor in the genesis of acute ischaemic arrhythmias.
Lin
Li
L
Department of Physiology, Second Military Medical University, Shanghai 200433, People's Republic of China.
Yuan
Wen-Jun
WJ
D000208:Acute Disease; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004562:Electrocardiography; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood / Q000378:metabolism*; D016232:Endothelins / Q000235:genetics; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D011498:Protein Precursors / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D016376:Oligonucleotides, Antisense; D009842:Oligopeptides; D011498:Protein Precursors; D044022:Receptor, Endothelin A; C087220:BQ 610