CARDIOPROTECTION BY RAMIPRILAT IN ISOLATED RABBIT HEARTS

The anti-ischemic properties of the ACE inhibitor ramiprilat (ram) wer e investigated in electrically driven Langendorff hearts from rabbits whose endogenous angiotensin-I content has been previously shown to be very low (constant pressure: 70 cm H2O, Tyrode solution, Ca2+ 1.8 mmo l/1). Cumulative concentration-response curves showed that the reducti on in global coronary flow (CF) by exogenous angiotensin-I was concent ration dependently inhibited by ram (P < 0.05). Myocardial ischemia (M I) was induced by occlusion of a left coronary artery branch and MI wa s quantified by NADH surface fluorescence photography. MI was signific antly enlarged (+23%) (P < 0.05) by exogenous angiotensin-I (6 x 10(-9 ) mol/1). Addition of ram (10(-8) mol/1) to the perfusion buffer simul taneously with angiotensin-I, completely prevented the reduction of CF by angiotensin-I (P > 0.05) and significantly diminished MI even belo w control values (-25%) (P < 0.05). In the absence of exogenous angiot ensin-1, ram alone (10(-8) mol/1) did not significantly enhance CF (P > 0.05), supporting findings demonstrating a very low endogenous angio tensin-I content in isolated rabbit hearts. However, ram alone (10(-8) mol/1) significantly diminished MI (-24%) (P < 0.05). We conclude tha t ram does possess direct cardioprotective properties that are indepen dent of the inhibition of angiotensin-II generation but that may be re lated to potentiation of the effects of bradykinin.