Protective action of angiotensin converting enzyme inhibitors on cardiac hypertrophy in the aortic-banded rat.
Imidapril, enalapril and quinapril were subcutaneously administered to aortic-banded rats by osmotic minipumps to compare the suppressive actions of these angiotensin converting enzyme (ACE) inhibitors on pressure-induced cardiac hypertrophy. Among the three drugs tested, imidapril was most potent for the prevention of cardiac hypertrophy, although equipotent hypotensive doses were used. Imidapril reduced both serum and cardiac ACE activities, while enalapril reduced only the former. Quinapril also reduced both, however, it was less potent at reducing the former compared to imidapril. Moreover, only imidapril significantly decreased left ventricular end diastolic pressure, which tended to be increased by aortic-banding. The lipophilicity of ACE inhibitors could not explain the more potent suppressive action of imidapril on cardiac hypertrophy because the lipophilicity of imidaprilat, an active metabolite of imidapril, was as low as an active metabolite of enalapril; i.e., much lower than an active metabolite of quinapril. The efficacy of ACE inhibitors on pressure-induced cardiac hypertrophy depends not only on an inhibitory effect on cardiac ACE activity, but also on other actions such as their effect on left ventricular end diastolic pressure.
Kurosawa
Y
Y
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Kojima
K
K
Kato
M
M
Ohashi
R
R
Minami
K
K
Narita
H
H
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D006332:Cardiomegaly / Q000503:physiopathology / Q000517:prevention & control*; D003971:Diastole; D004656:Enalapril / Q000494:pharmacology; D006321:Heart / Q000033:anatomy & histology / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007546:Isoquinolines / Q000494:pharmacology; D000077583:Quinapril; D051381:Rats; D044005:Tetrahydroisoquinolines; D016277:Ventricular Function, Left / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D004656:Enalapril; C065166:imidapril; D000077583:Quinapril