The role of prostaglandin synthesis stimulation in the protective effect of captopril on ischaemia-reperfusion arrhythmias in rats in vivo.
Attenuation of ischaemia-reperfusion induced arrhythmias by several angiotensin converting enzyme (ACE) inhibitors, such as captopril, has been demonstrated. The role of prostaglandin synthesis stimulation in this protective effect of ACE inhibition was evaluated in an in vivo rat model. To produce arrhythmia, the left main coronary artery was occluded for 7 min, followed by 7 min of reperfusion. Captopril (3 mg kg-1) and a prostaglandin synthesis inhibitor, indomethacin (2 mg kg-1) alone or together were administered by intravenous (i.v.) injection 10 min before occlusion. Captopril reduced the incidence of ventricular tachycardia (VT) and the number of ventricular ectopic beats (VEB) on ischaemia and reperfusion as well as the incidence of reversible ventricular fibrillation (VF) on reperfusion. These protective effects of captopril against ischaemia-reperfusion-induced arrhythmias were prevented by indomethacin. Captopril also caused a sustained decrease of preocclusion values in the arterial blood pressure (BP) and heart rate (HR), whereas in the presence of indomethacin, captopril had no significant effect on either HR or arterial BP values except the heart rate value just before occlusion. Indomethacin alone did not affect either the severity of arrhythmias or the haemodynamic parameters. These results suggest that, in this experimental model, the protective effects of ACE inhibitors on the arrhythmias following ischaemia-reperfusion are mediated by the stimulation of prostaglandin synthesis and the haemodynamic effects of these drugs may have a contributory role in their protective effect.
Birincioglu
M
M
Department of Pharmacology, Faculty of Medicine, Inönü University, Malatya, Turkey.
Olmez
E
E
Aksoy
T
T
Acet
A
A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D002216:Captopril; D007213:Indomethacin