Antiarrhythmic effect of endothelin-A receptor antagonist on acute ischemic arrhythmia in isolated rat heart.
OBJECTIVE
To observe the effects of endothelin receptor subtype A (ETA) and B (ETB) antagonists on acute ischemic arrhythmia in isolated rat heart, and to determine whether endogenous endothelin (ET) was implicated in the pathophysiological process of arrhythmia induced by acute myocardial ischemia.


METHODS
Fifty-three SD male rats were randomized into 8 groups. Heart was isolated and perfused in Langendorff mode and acute ischemia model was established by ligation of the left anterior descending (LAD) coronary artery. The effects of ETA receptor antagonist PD156707 and ETB receptor antagonist IRL1038 on arrhythmia, heart function, the myocardial activity of superoxide dismutase (SOD), and the content of melondialdehyde (MDA) during the acute 60-min ischemic phase were analyzed.


RESULTS
Pretreatment with PD156707 (20-500 nmol/L) dose-dependently improved the ischemic isolated heart function, enhanced SOD activity and decreased MDA content in the ischemic myocardium, and suppressed the acute ischemic arrhythmia. Conversely pretreatment with IRL1038 did not change the heart function, SOD activity, MDA content, and the acute ischemic arrhythmia significantly as compared with the occlusion control.


CONCLUSIONS
ETA receptor antagonist effectively improved heart function, enhanced anti-oxidative function of the myocardium and reduced arrhythmia during the acute ischemic phase in isolated rat hearts, while ETB receptor antagonist did not exert protective effects, suggesting that endogenous ET-1, acting through ETA receptor, may be one of the factors implicated in arrhythmia and impairment to heart function during the acute ischemic phase.
Xu
Hong
H
Department of Physiology, Second Military Medical University, Shanghai 200433, China.
Lin
Li
L
Yuan
Wen-Jun
WJ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000517:prevention & control; D003326:Coronary Circulation / Q000187:drug effects; D004149:Dioxoles / Q000494:pharmacology* / Q000627:therapeutic use; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D017202:Myocardial Ischemia / Q000150:complications*; D009206:Myocardium / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013482:Superoxide Dismutase / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D004149:Dioxoles; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; C093321:PD 156707; D010446:Peptide Fragments; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C077420:Cys(11)-Cys(15)-endothelin-1 (11-21); D008315:Malondialdehyde; D013482:Superoxide Dismutase