Effects of the angiotensin-converting enzyme inhibitor enalapril on sympathetic neuronal function and beta-adrenergic desensitization in heart failure after myocardial infarction in rats.
One of the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure may derive from sympathoinhibition and the prevention of beta-adrenergic desensitization. However, the roles of these properties in the overall effects of ACE inhibitor are not clear. We studied the effects of chronic enalapril treatment (20 mg/L in drinking water for 12 weeks) on left ventricular (LV) function, cardiac norepinephrine (NE), sympathetic neuronal function assessed by 131I-metaiodobenzylguanidine (MIBG), beta-receptors, and isometric contraction of papillary muscle in rats with myocardial infarction (MI) induced by coronary artery ligation. Decreased LV function in the MI rats was associated with reduced cardiac NE content and MIBG uptake, and severely blunted responses of non-infarcted papillary muscle to isoproterenol, forskolin, and calcium. Enalapril attenuated LV remodeling in association with a reduction of the ventricular loading condition and restored baseline developed tension of non-infarcted papillary muscle to the level of sham-operated rats. However, enalapril did not improve cardiac NE content, MIBG uptake, or inotropic responsiveness to beta-agonists. These results suggest that the major effect of the ACE inhibitor enalapril in the treatment of heart failure is not due to sympathoinhibition or restoration of beta-adrenergic pathway in this model of heart failure.
Igawa
Akihiko
A
2nd Department of Internal Medicine, Toyama Medical & Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Nozawa
Takashi
T
Yoshida
Naohiro
N
Fujii
Nozomu
N
Kato
Bun-ichi
B
Inoue
Minoru
M
Tazawa
Shusaku
S
Yamada
Yoshihisa
Y
Asanoi
Hidetsugu
H
Inoue
Hiroshi
H
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D004656:Enalapril / Q000494:pharmacology*; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010210:Papillary Muscles / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
D000806:Angiotensin-Converting Enzyme Inhibitors; D011943:Receptors, Adrenergic, beta; D004656:Enalapril; D009638:Norepinephrine