Enalaprilat attenuates ischemic rises in intracellular sodium in the isolated rat heart via the bradykinin receptor

Purpose: Angiotensin-converting enzyme (ACE) inhibitors have been shown to have beneficial effects on ischemic myocardium. We examined whether rite AC E inhibitor: enalaprilat (EN), improves intracellular sodium homeostasis du ring myocardial ischemia and the relationship of this effect to bradykinin. Methods: EN (3.2 nM) was administered to isolated rat hearts that were sub jected to ischemia and reperfusion. Intracellular sodium and pH were monito red using magnetic resonance spectroscopy? (MRS). The specific bradykinin B 2 receptor antagonist, HOE 140 (10 nM), was administered with EN in some he arts to determine the effects of bradykinin blockade on EN-mediated effects . Results: EN blunted the rise in ischemic intracellular sodium, measured u sing MRS. With reperfusion, EN-treated hearts recovered 80% of their preisc hemic ventricular function, compared with negligible recovery in controls. These beneficial effects of EN were blocked when the bradykinin receptor an tagonist, HOE 140, was coadministered with EN. HOE 140 also blocked EN-medi ated attenuation of ischemic intracellular acidosis. Conclusions: These res ults suggest that EN exerts beneficial effects on ischemic intracellular so dium and pH homeostasis via the bradykinin receptor These effects of EN may provide a mechanism for the beneficial actions of this agent during isc he min.