Cardioprotection by ramiprilat in isolated rabbit hearts.
The anti-ischemic properties of the ACE inhibitor ramiprilat (ram) were 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 mmol/l). Cumulative concentration-response curves showed that the reduction in global coronary flow (CF) by exogenous angiotensin-I was concentration dependently inhibited by ram (P < 0.05). Myocardial ischemia (MI) was induced by occlusion of a left coronary artery branch and MI was quantified by NADH surface fluorescence photography. MI was significantly enlarged (+23%) (P < 0.05) by exogenous angiotensin-I (6 x 10(-9) mol/l). Addition of ram (10(-8) mol/l) to the perfusion buffer simultaneously with angiotensin-I, completely prevented the reduction of CF by angiotensin-I (P > 0.05) and significantly diminished MI even below control values (-25%) (P < 0.05). In the absence of exogenous angiotensin-I, ram alone (10(-8) mol/l) did not significantly enhance CF (P > 0.05), supporting findings demonstrating a very low endogenous angiotensin-I content in isolated rabbit hearts. However, ram alone (10(-8) mol/l) significantly diminished MI (-24%) (P < 0.05). We conclude that ram does possess direct cardioprotective properties that are independent of the inhibition of angiotensin-II generation but that may be related to potentiation of the effects of bradykinin.
Rump
A F
AF
Institut für Pharmakologie, Universität Köln, Germany.
Koreuber
D
D
Rösen
R
R
Klaus
W
W
D000803:Angiotensin I / Q000037:antagonists & inhibitors*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism / Q000517:prevention & control*; D009243:NAD / Q000378:metabolism; D011817:Rabbits; D017257:Ramipril / Q000031:analogs & derivatives* / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D009243:NAD; C052549:ramiprilat; D000803:Angiotensin I; D017257:Ramipril