Cardioprotective Effects of Enalapril in Acute Myocardial Ischemia

Abstract

Enalapril, a new potent orally active angiotensin-converting enzyme inhibitor, was studied in cats subjected to acute myocardial ischemia. Enalapril, administered intravenously (2 mg/kg, plus 2 mg/kg/h) 30 min after ligation of the left coronary artery, significantly reduced the pressure-rate index, an indicator of myocardial oxygen demand. This was confirmed in isolated cat papillary muscles where enalapril reduced contractile force by 5–10%. During myocardial ischemia, enalapril reversed the elevated S-T segment of the electrocardiogram toward normal 2 h after the onset of ischemia. Moreover, enalapril significantly blunted the increases in circulating creatine kinase (CK) activity, as well as significantly prevented the loss in myocardial CK activity. These changes correlated with reduced myocardial loss of compounds containing free amino-nitrogen. Enalapril effectively acted as a converting enzyme inhibitor over the 5-hour course of the observation period. However, enalapril also acted as an angiotensin antagonist in isolated coronary arteries, a finding that may help explain its efficacy in myocardial ischemia. Enalapril did not appear to stabilize the membranes of cat liver lysosomes, and thus probably does not protect the ischemic myocardium by lysosomal stabilization.

Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent

“…It is well established that both H 2 S and NO exert potent cytoprotective effects in the setting of cardiovascular disease in various animal model systems (5,7,(13)(14)(15). In addition, H 2 S has been reported to be cytoprotective in some organ systems, such as the central nervous system and gastrointestinal tract, independent of NO (3,11,(16)(17)(18).…”

Comparison of the effects of EXP3174, an angiotensin II antagonist and enalaprilat on myocardial infarct size in anaesthetized dogs

“…It has been shown that blockade of the renin-angiotensin system by captopril (Ertl et al, 1982), enalapril (Lefer & Peck, 1984;Hock et al, 1985), and ramipril (Martorana et al, 1990) produces a beneficial effect in myocardial ischaemia. However, this cardioprotective effect of angiotensin Iconverting enzyme inhibitors (ACEIs) is not universally recognized, as Liang et al (1982) and Daniell et al (1984) have failed to demonstrate any myocardial protection with ACEIs.…”

“…However, several experiments suggest that the anti-ischaemic effect of the sulphydryl-containing ACEI captopril could be due to non specific effects of this drug, such as an inhibition of oxygen free radical-dependent reperfusion injury (Westlin & Mullane, 1988;Chopra et al, 1992) and/or an interference with arachidonic acid metabolism (Van Gilst et al, 1987). However, in some experimental models of ischaemia, acute administration of non sulphydryl-containing ACEIs also limited infarct size in rats (Hock et al, 1985) and in cats (Lefer & Peck, 1984). Differences in animal models, duration and severity of ischaemia, occurrence of reperfusion, and drug concentrations could contribute to these conflicting results.…”

Enalaprilat Improves the Impaired Left Ventricular Pump Function during Exercise in Hypertensives with Coronary Microangiopathy and with Coronary Artery Disease

“…Enalaprilat is an antagonist of angiotensin II in isolated coronary arteries [44] and antagonizes the coronary vasoconstrictor effect of angiotensin II [45]. It has been shown [18,19] that the renin-angiotensin system can be abruptly and completely blocked by an intravenous bolus injection of enalaprilat with a rapid improvement of cardiac performance in patients with chronic heart failure, achieving the peak effect within 30 min.…”