title: Cardioprotective effects of bosentan, a mixed endothelin type A and B receptor antagonist, during myocardial ischaemia and reperfusion in rats.
abstract: The present study evaluated the cardioprotective potential of bosentan, a mixed endothelin type A and B receptor antagonist, in the myocardial ischaemia-reperfusion model of myocardial infarction. Adult male wistar rats (175-225 g) were divided into three groups: sham operated, non-myocardial ischaemia-reperfusion (SHAM); saline-treated myocardial ischaemia-reperfusion control (CON); bosentan-treated myocardial ischaemia-reperfusion (BOS). All animals were anaesthetized and subjected to 40 min. occlusion of left anterior descending coronary artery followed by 120 min. of reperfusion. Saline or drug was administered to the CON or BOS group, respectively, 20 min. after the left anterior descending coronary artery occlusion. Haemodynamic parameters viz. systolic arterial pressure, diastolic arterial pressure and heart rate were recorded throughout the experimental period. Hearts were subsequently excised and processed for histopathological and infarct size evaluation and for biochemical estimation of cardiac specific enzyme creatine kinase-MB (CK-MB) and myocardial malondialdehyde, a lipid peroxidation marker. Myocardial ischaemic reperfusion resulted in severe myocardial injury, depression of haemodynamic function, significant increase in malondialdehyde levels and decline in CK-MB isoenzyme activity in the heart tissue. Administration of bosentan (3 mg/kg, intravenously) slightly improved haemodynamic effects, decreased myocardial oxygen consumption, significantly (P<0.01) attenuated the rise in malondialdehyde levels and loss of myocardial CK-MB isoenzyme activity compared to the CON group, whereas bosentan administration significantly reduced the percentage area of fiber loss and infarct area. It is therefore concluded that endothelin-1 may mediate myocardial damage produced by ischaemia and reperfusion and that dual blockade of endothelinA and endothelinB receptors may have potential as a mode of therapy for myocardial infarction.
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, New Delhi-110 029, India. dsarya16@hotmail.com
authors.forename: Arya Dharamvir
authors.initials: AD
authors.lastname: Singh
authors.forename: Saxena
authors.initials: S
authors.lastname: Amit
authors.forename: Ojha Shreesh
authors.initials: OS
authors.lastname: Kumar
authors.forename: Mittal
authors.initials: M
authors.lastname: Rajan
authors.forename: Nandave
authors.initials: N
authors.lastname: Mukesh
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D000077300:Bosentan; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003402:Creatine Kinase / Q000378:metabolism; D003971:Diastole / Q000502:physiology; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D006339:Heart Rate / Q000502:physiology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology*; D016019:Survival Analysis; D013599:Systole / Q000502:physiology; D013997:Time Factors
chemical_list: D002316:Cardiotonic Agents; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D013449:Sulfonamides; D008315:Malondialdehyde; D003402:Creatine Kinase; D000077300:Bosentan