Prolonging action of imidapril on the lifespan expectancy of cardiomyopathic hamsters.
We studied the effect of imidapril, a novel angiotensin-converting enzyme (ACE) inhibitor, on lifespan expectancy of cardiomyopathic (CM) hamsters of BIO 14.6 strain, one of the representative models of congestive heart failure (CHF). Imidapril was consecutively administered to hamsters by mixing it in their diet at a concentration of 480 ppm (approximately 30 mg/kg/day) or 1,600 ppm (approximately 120 mg/kg/day) from age 26 weeks. Only several control hamsters died before age 54 weeks, but their survival rate decreased to 23.7% at age 73 weeks. The survival rates of 480-ppm and 1,600-ppm imidapril groups at age 73 weeks were as high as 75.7 and 68.4%, respectively (p < 0.01 vs. control hamsters). Macroscopic and microscopic pathology in imidapril-treated groups was milder than that in control animals in general, but differences were not statistically significant when animals were divided into survivors and fatalities except for the presence of mural thrombus in the heart. We further studied the effects of imidapril on blood pressure (BP), in vivo cardiac function, cardiac beta-adrenoceptor distribution, and plasma catecholamine levels after dietary treatment with 480 ppm imidapril for 8-10 weeks from age 37 weeks. Imidapril-treated animals showed improved cardiac function under urethane anesthesia. These results indicate that imidapril prolongs lifespan expectancy of CM hamsters and suggest that a hemodynamic effect of imidapril is involved in its beneficial effect.
Narita
H
H
Pharmaceutical Development Research Laboratory, Saitama, Japan.
Kaburaki
M
M
Doi
H
H
Ogiku
N
N
Yabana
H
H
Kurosawa
H
H
Ohmachi
Y
Y
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D009202:Cardiomyopathies / Q000188:drug therapy*; D006224:Cricetinae; D004298:Dopamine / Q000097:blood; D004837:Epinephrine / Q000097:blood; D004983:Ethanolamines / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D048289:Imidazolidines; D008017:Life Expectancy; D008099:Liver / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine / Q000097:blood; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015996:Survival Rate
D000318:Adrenergic beta-Agonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D004983:Ethanolamines; D007093:Imidazoles; D048289:Imidazolidines; D011943:Receptors, Adrenergic, beta; C025342:RP333; C065166:imidapril; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine