Induction of cardiac angiotensinogen mRNA and angiotensin converting enzyme (ACE) activity in isoproterenol-induced heart injury.
Effects of isoproterenol (ISO) on the expression of cardiac angiotensinogen mRNA, angiotensin converting enzyme (ACE) activity, and mechanical functions in spontaneously hypertensive rats were investigated. In the acute phase, defined as within 24 h after the subcutaneous injection of ISO 85 mg/kg, cardiac angiotensinogen mRNA was slightly induced, but ACE activity was not. In the subacute phase, defined as within 8 d after ISO treatment on 2 successive d, both angiotensinogen mRNA expression and ACE activity in the heart were markedly induced. ACE activity in serum was not affected by ISO in either phase. In the subacute phase, ISO reduced body weight and blood pressure, increased ventricular weight and calcium content, and impaired cardiac mechanical function. Oral treatment with imidapril (10 mg/kg/d), an ACE inhibitor, 1 h before each ISO treatment and on the following 6 d, improved ventricular hypertrophy, the elevation of the left ventricular end diastolic pressure, the reduction in contractility, and the prolongation of the time constant. Imidapril significantly suppressed both serum and cardiac ACE activity but did not affect cardiac angiotensinogen mRNA expression in the subacute phase. These results indicate that enhancement of cardiac angiotensinogen mRNA and ACE activity is involved in ISO-induced cardiac dysfunction. Imidapril improved ISO-induced cardiac dysfunction, possibly by suppression of the local ACE activity as well as circulating ACE activity.
Lead Generation Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
N
N
Ogiku
R
R
Ishida
K
K
Saeki
M
M
Sugiura
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000808:Angiotensinogen / Q000096:biosynthesis*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D007093:Imidazoles / Q000008:administration & dosage*; D048289:Imidazolidines; D007545:Isoproterenol / Q000008:administration & dosage*; D009206:Myocardium / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D002316:Cardiotonic Agents; D007093:Imidazoles; D048289:Imidazolidines; D012333:RNA, Messenger; D000808:Angiotensinogen; C065166:imidapril; D007703:Peptidyl-Dipeptidase A; D007545:Isoproterenol