THE ROLE OF PROSTAGLANDIN SYNTHESIS STIMULATION IN THE PROTECTIVE EFFECT OF CAPTOPRIL ON ISCHEMIA-REPERFUSION ARRHYTHMIAS IN RATS IN-VIVO

Attenuation of ischaemia-reperfusion induced arrhythmias by several an giotensin converting enzyme (ACE) inhibitors, such as captopril, has b een demonstrated. The role of prostaglandin synthesis stimulation in t his protective effect of ACE inhibition was evaluated in an in vivo ra t model. To produce arrhythmia, the left main coronary artery was occl uded 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 ventricula r tachycardia (VT) and the number of ventricular ectopic beats (VEE) o n ischaemia and reperfusion as well as the incidence of reversible ven tricular fibrillation (VF) on reperfusion. These protective effects of captopril against ischaemia-reperfusion-induced arrhythmias were prev ented by indomethacin. Captopril also caused a sustained decrease of p reocclusion values in the arterial blood pressure (BP) and heart rate (HR), whereas in the presence of indomethacin, captopril had no signif icant 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 resu lts suggest that, in this experimental model, the protective effects o f ACE inhibitors on the arrhythmias following ischaemia-reperfusion ar e mediated by the stimulation of prostaglandin synthesis and the haemo dynamic effects of these drugs may have a contributory role in their p rotective effect. (C) 1997 The Italian Pharmacological Society.