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?

Abstract

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.

Role of bradykinin in preconditioning and protection of the ischaemic myocardium

“…Indeed, it has been proposed that ACE inhibitors, such as captopril, that possess sulfhydryl moieties are able to act as scavengers or reactive oxygen species and as a consequence are protective when administered alone (Anderson et al, 1996). However, the picture is complicated by the fact that some ACE inhibitors that do not possess a sulphydryl group have been reported to be cardioprotective in some models (Birincioglu et al, 1997;Matoba et al, 1999). Matoba et al (1999) showed that cilazaprilat, a non-sulfhydryl containing ACE inhibitor, protected directly against hypoxia-reoxygenation injury in cultured rat myocytes and enhanced bradykinin production in the culture media of the myocytes.…”

Captopril suppresses inflammation in endotoxin-induced uveitis in rats

“…ACE inhibitors including captopril have proven to be beneficial in experimental autoimmune encephalomyelitis (Constantinescu et al, 1995), myocarditis (Godsel et al, 2003), adriamycin-induced myocardial and hematological toxicities (O. Al-Shabanah et al, 1998), Freund`s adjuvant arthritis (Agha and Mansour, 2000) and experimental rats` colitis (Jahovic et al, 2005). The ability of captopril to act as a reactive oxygene species (ROS) scavenger (Mira et al, 1993) was found to be of major importance in its protection against ischemia-reperfusion-induced arrhythmias (Birincioglu et al, 1997) and liver injury in rats (Gulluoglu et al, 1996). An anti-tumor, antifibrotic and cytoprotective effects of captopril have also been demonstrated (Williams et al, 2005;Regan et al, 1996;Murley et al, 2004).…”

The effects of enalapril maleate and cold stress exposure on tyrosine hydroxylase activity in some rat tissues

“…[1][2][3] Angiotensin-II elevates the release of norepinephrine from terminal adrenergic neurons. 3,4 Moreover, angiotensin-II elevates the release of epinephrine and norepinephrine from adrenal medulla and stimulates the autonomic ganglions in the peripheral autonomic nerve system. 1,4,5 Tyrosine hydroxylase (TH) is an enzyme which plays a central role in neurotransmission and hormonal function of catecholamines.…”

“…Experimental studies have shown that angiotensin-convertingenzyme inhibitors have positive effects on the circulation. Enalapril maleate, which is an angiotensin converting enzyme inhibitor, is used as an antihypertensive drug and blocks angiotensin-I conversion to angiotensin-II [1][2][3] by its action on angiotensin converting enzyme (ACE). [1][2][3] Angiotensin-II elevates the release of norepinephrine from terminal adrenergic neurons.…”

“…Enalapril maleate, which is an angiotensin converting enzyme inhibitor, is used as an antihypertensive drug and blocks angiotensin-I conversion to angiotensin-II [1][2][3] by its action on angiotensin converting enzyme (ACE). [1][2][3] Angiotensin-II elevates the release of norepinephrine from terminal adrenergic neurons. 3,4 Moreover, angiotensin-II elevates the release of epinephrine and norepinephrine from adrenal medulla and stimulates the autonomic ganglions in the peripheral autonomic nerve system.…”