Enalaprilat attenuates ischemic rises in intracellular sodium in the isolated rat heart via the bradykinin receptor.
OBJECTIVE
Angiotensin-converting enzyme (ACE) inhibitors have been shown to have beneficial effects on ischemic myocardium. We examined whether the ACE inhibitor, enalaprilat (EN), improves intracellular sodium homeostasis during myocardial ischemia and the relationship of this effect to bradykinin.


METHODS
EN (3.2 nM) was administered to isolated rat hearts that were subjected to ischemia and reperfusion. Intracellular sodium and pH were monitored using magnetic resonance spectroscopy (MRS). The specific bradykinin B2 receptor antagonist, HOE 140 (10 nM), was administered with EN in some hearts to determine the effect of bradykinin blockade on EN-mediated effects.


RESULTS
EN blunted the rise in ischemic intracellular sodium, measured using MRS. With reperfusion, EN-treated hearts recovered 80% of their preischemic ventricular function, compared with negligible recover, in controls. These beneficial effects of EN were blocked when the bradykinin receptor antagonist, HOE 140, was coadministered with EN. HOE 140 also blocked EN-mediated attenuation of ischemic intracellular acidosis.


CONCLUSIONS
These results suggest that EN exerts beneficial effects on ischemic intracellular sodium and pH homeostasis via the bradykinin receptor. These effects of EN may provide a mechanism for the beneficial actions of this agent during ischemia.
Whang
J
J
Heart and Vascular Institute/MAC, Morristown, New Jersey 07960-0615, USA. jw64@home.com
Ramasamy
R
R
Dizon
J M
JM
Bergmann
S R
SR
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D046508:Culture Techniques; D015773:Enalaprilat / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D007424:Intracellular Fluid / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D018002:Receptors, Bradykinin / Q000187:drug effects* / Q000502:physiology; D012964:Sodium / Q000378:metabolism*
D018002:Receptors, Bradykinin; C065679:icatibant; D012964:Sodium; D015773:Enalaprilat; D001920:Bradykinin