Cardioprotective effects of benazepril, an angiotensin-converting enzyme inhibitor, in an ischaemia-reperfusion model of myocardial infarction in rats.
The present study evaluated the effects of benazepril, an angiotensin-converting enzyme inhibitor on haemodynamic, biochemical, and immunohistochemical (Bax and Bcl-2 protein) indices in ischaemia and reperfusion (IR) injury.



Male Wistar albino rats were divided into three groups and were orally administered saline once daily (IR-sham and IR-control) or benazepril (30 mg/kg/day; IR-benazepril) for 14 days. On the 15(th) day, in the IR-control and IR-benazepril groups, rats were subjected to left anterior descending coronary artery occlusion for 45 minutes followed by a one-hour reperfusion. Haemodynamic parameters were recorded and rats were sacrificed; hearts were isolated for biochemical estimation and immunohistochemistry.



In the IR-control group, significant ventricular dysfunctions (p<0.05 vs. IR-sham group) were observed along with enhanced expression of pro-apoptotic protein Bax. A decline in lactate dehydrogenase activity and increased content of thiobarbituric acid reactive substances, a marker of lipid peroxidation, were observed. Benazepril pretreatment significantly improved mean arterial pressure (p<0.01), reduced left ventricular end-diastolic pressure (p<0.05), and improved both inotropic and lusitropic function of the heart (+LVdP/dt and - LVdP/dt) (p<0.05; p<0.01) as compared to IR-control. Furthermore, benazepril treatment significantly decreased the level of thiobarbituric acid reactive substances and restored the activity of lactate dehydrogenase towards normal value (p<0.05 vs. IR-control).



This study demonstrates that benazepril upregulated Bcl-2 protein and decreased Bax protein expression, thus exhibiting anti-apoptotic effects. These beneficial effects of benazepril will have an important implication in the therapeutic use of benazepril in ischaemic heart disease.
Charan Sahoo
Kanhei
K
Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nager, New Delhi-110029, India.
Arora
Sachin
S
Goyal
Sameer
S
Kishore
Kamal
K
Ray
Ruma
R
Nag
Tapas Chandra
TC
Singh Arya
Dharamvir
D
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001552:Benzazepines / Q000627:therapeutic use*; D015870:Gene Expression / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009203:Myocardial Infarction / Q000201:enzymology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D008315:Malondialdehyde; C044946:benazepril