Deleterious effect of exogenous angiotensin-I on the extent of regional ischaemia and its inhibition by captopril.
The endogenous activity of the local renin-angiotensin system (RAS) and the anti-ischaemic properties of captopril were investigated in electrically driven rabbit Langendorff hearts (constant pressure: 70 cmH2O, Tyrode solution, Ca2+ 1.8 mmol.l-1). Cumulative concentration-response curves showed no significant difference (P > 0.05) between the reduction of the global coronary flow (CF) by exogenous angiotensin-I or angiotensin-II (EC50 = 10(-10) mol.l-1). It is concluded that the local RAS in isolated rabbit hearts is highly sensitive, whereas its endogenous activity is very low due to very low endogenous angiotensin-I content. Myocardial ischaemia (MI) was induced by the occlusion of a left coronary artery branch and MI was quantified from NADH surface fluorescence photography. MI was significantly enlarged (+35%) (P < 0.05) by exogenous angiotensin-I (6 x 10(-9) mol.l-1). The reduction in CF and the increment in MI by angiotensin-I could be completely prevented by adding captopril at a low concentration (10(-6) mol.l-1) to the perfusion buffer. In the absence of exogenous angiotensin-I, captopril alone (10(-6) mol.l-1) neither significantly enhanced CF (P > 0.05), nor diminished MI (P > 0.05), supporting the finding of very low endogenous activity of the local RAS in this model. We, moreover, conclude that at a low concentration (10(-6) mol.l-1) captopril does not possess direct cardioprotective properties independent of its ACE inhibiting action.
Rump
A F
AF
Institut für Pharmakologie, Universität Köln, Germany.
Rösen
R
R
Korth
A
A
Klaus
W
W
D000803:Angiotensin I / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009243:NAD / Q000378:metabolism; D009924:Organ Culture Techniques; D011817:Rabbits; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
D009243:NAD; D000803:Angiotensin I; D002216:Captopril