Infarct size limiting effect of apstatin alone and in combination with enalapril, lisinopril and ramipril in rats with experimental myocardial infarction.
Bradykinin is a potent vasoactive peptide that is known to elicit a number of biological responses. A number of peptidases have been identified to possess kininase activity, the inhibition of which increases the availability and effectiveness of kinins. We wished to determine the cardioprotective actions of an aminopeptidase P inhibitor, apstatin alone and in combination with enalapril/lisinopril/ramipril in an in vivo rat model of acute ischemia (30 min) and reperfusion (4 h). 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 using the staining agent 2,3,5-triphenyl tetrazolium chloride (TTC). Lipid peroxide levels in serum and in heart tissue were estimated spectrophotometrically. A lead II electrocardiogram was monitored at various intervals throughout the experiment. Infarct size was reduced to a greater extent with apstatin and with combined inhibition it was further reduced. Infarct size reduction obtained with the combined inhibition came to normal with the prior administration of B2 bradykinin antagonist HOE140 suggests the involvement of bradykinin in the cardioprotective actions of apstatin.
Veeravalli
K K
KK
Pharmacology Division, Department of Pharmaceutical Sciences, Andhra University, Visakhapatnam 530 003, Andhra Pradesh, India.
Akula
A
A
Routhu
K V
KV
Kota
M K
MK
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D065168:Bradykinin Receptor Antagonists; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008054:Lipid Peroxides / Q000032:analysis / Q000097:blood; D017706:Lisinopril / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008315:Malondialdehyde / Q000032:analysis / Q000097:blood; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000503:physiopathology; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D017257:Ramipril / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D065168:Bradykinin Receptor Antagonists; D008054:Lipid Peroxides; D010455:Peptides; D008315:Malondialdehyde; D004656:Enalapril; C065679:icatibant; D017706:Lisinopril; C097277:apstatin; D017257:Ramipril; D001920:Bradykinin