lisinopril and Necrosis

The cardioprotective involvement of bradykinin was evaluated using the ACE inhibitor, lisinopril, and the APP inhibitor, 2-mercaptoethanol alone and in combination in rats with experimental myocardial infarction. The signal cascade mechanism mediating the cardioprotective actions of bradykinin was evaluated by administering aspirin and methylene blue prior to lisinopril and 2-mercaptoethanol combined treatment. Myocardial infarction was produced by occlusion of the left anterior descending coronary artery for 30 min followed by 4 h of reperfusion. Infarct size was measured by the TTC stain method. Serum free radical levels were estimated by the method developed by Yagi. A lead II electrocardiogram was monitored throughout the experiment. With the combined inhibition of both the enzymes ACE and APP, a better cardioprotection was observed. The observed cardioprotection was decreased with the prior administration of aspirin and methylene blue. The results suggest the cardioprotective role of bradykinin during experimental myocardial infarction. The results are further suggesting the involvement of both prostaglandins and nitric oxide pathways in the cardioprotective actions of bradykinin.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Aspirin; Bradykinin; Female; Heart Ventricles; Lisinopril; Male; Mercaptoethanol; Methylene Blue; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Necrosis; Nitric Oxide; Prostaglandin Antagonists; Rats; Rats, Wistar; Signal Transduction

High-density angiotensin-converting enzyme (ACE) binding is present in heart valve leaflets and the fibrous tissue that appears in the rat myocardium after either chronic administration of angiotensin II (AngII) or after myocardial infarction. This suggests that connective tissue ACE is independent of circulating AngII and that ACE may be an integral component of normal and pathologic tissue repair. To address this possibility the present study was undertaken. We sought to determine whether the ACE inhibitor lisinopril would attenuate fibrous tissue ACE binding and fibrous tissue formation in the myocardium of rats receiving AngII. Three experimental groups were examined: untreated, age-matched controls; rats receiving subcutaneous AngII (150 ng/min) by minipump for 2 weeks; and rats receiving AngII plus oral lisinopril (20 mg/kg/day) for 2 weeks. Cardiac ACE binding density was localized and quantified by in vitro autoradiography with [125I]-labeled 351A, a tyrosyl derivative of lisinopril, while fibrosis was identified by light microscopy in serial sections stained with picrosirius red. Hematoxylin and eosin and anti-fibronectin antibody were used to identify cardiac myocyte necrosis. Immunohistochemical labeling with alpha-smooth muscle actin was used to identify myofibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Autoradiography; Fibrosis; Immunohistochemistry; Lisinopril; Male; Myocardium; Necrosis; Peptidyl-Dipeptidase A; Rats; Rats, Sprague-Dawley

The aims were to determine: (1) if angiotensin converting enzyme (ACE) inhibition and angiotensin II receptor blockade can prevent angiotensin II induced coronary vascular damage; (2) if the cardioprotective properties of ACE inhibition are dose dependent; and (3) if the cardioprotective properties of ACE inhibition are independent of its ability to prevent the conversion of angiotensin I to angiotensin II.. Control rats and rats with either renovascular hypertension or continuous angiotensin II infusion (150 ng.min-1) for 14 d were subdivided into nine groups as follows: unoperated and untreated controls (n = 5); untreated renovascular hypertension (n = 8); untreated angiotensin II (n = 9); a renovascular hypertension group receiving one of the following doses of lisinopril 20 (n = 8), 2.5 (n = 4), and 0.6 (n = 6) mg.kg-1.d-1; a renovascular hypertension group receiving losartan (7.5 mg.d-1, n = 4); and an angiotensin II group receiving either the high dose of lisinopril (n = 6) or losartan (n = 4). Treatment was started one day before initiation of renovascular hypertension and angiotensin II infusion and continued throughout the study period. The number and size of necrotic areas and numbers of damaged coronary vessels were determined in sections of right and left ventricular tissue.. Both coronary vascular injury and myocyte injury induced by angiotensin II were prevented by losartan. In renovascular hypertension, the lowest dose of lisinopril prevented vascular and attenuated myocyte damage but to a lesser degree than the higher doses. The cardioprotective ability of ACE inhibition is primarily the result of its ability to prevent the conversion of angiotensin I to angiotensin II.. Angiotensin II related cardiomyocyte necrosis and coronary vascular damage are angiotensin type 1 receptor mediated and completely preventable with the receptor antagonist losartan. The ability of ACE inhibition to prevent this damage is dose dependent and primarily related to the degree to which the inhibitor can prevent the conversion of angiotensin I to angiotensin II.

Topics: Angiotensin I; Angiotensin II; Animals; Biphenyl Compounds; Coronary Vessels; Dose-Response Relationship, Drug; Heart; Hypertension, Renovascular; Imidazoles; Lisinopril; Losartan; Male; Necrosis; Rats; Rats, Sprague-Dawley; Tetrazoles