Protective effect of ACE inhibitors on ischemia-reperfusion-induced arrhythmias in rats: is this effect related to the free radical scavenging action of these drugs?
The antiarrhythmic effects of captopril, a sulphydryl-containing angiotensin converting enzyme (ACE) inhibitor, were compared with those of the nonsulphydryl-containing ACE inhibitor lisinopril and the sulphydryl-containing agent glutathione in an in vivo rat model of coronary artery ligation. 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 lisinopril (0.1, 0.3 or 1 mg kg-1) caused marked decreases in mean arterial blood pressure (BP) and heart rate, whereas glutathione (5 mg kg-1) had no effect on them. The incidence of ventricular tachycardia (VT) on ischemia and reperfusion was significantly reduced by captopril and lisinopril. Captopril and 1 mg kg-1 lisinopril also significantly decreased the number of VEB during occlusion and the duration of VT on reperfusion, respectively. These drugs also attenuated the incidence of reversible ventricular fibrillation (VF) and the number of ventricular ectopic beats (VEB) during reperfusion. However, glutathione only reduced the incidence of VT on reperfusion, significantly. These results suggest that, in this experimental model, ACE inhibitors limit the arrhythmias following ischemia-reperfusion and free radical scavenging action of these drugs does not have a major contributory role in their protective effect.
Birincioglu
M
M
Department of Pharmacology, Faculty of Medicine, Inönü University, Malatya, Turkey.
Aksoy
T
T
Olmez
E
E
Acet
A
A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D005609:Free Radicals; D005978:Glutathione / Q000008:administration & dosage*; D017706:Lisinopril / Q000008:administration & dosage*; D008297:Male; D017202:Myocardial Ischemia; D015428:Myocardial Reperfusion Injury; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D005609:Free Radicals; D017706:Lisinopril; D005978:Glutathione