Beneficial effects of angiotensin-converting enzyme inhibition in adriamycin-induced cardiomyopathy in hamsters.
This study was performed to determine whether angiotensin (Ang) II-forming enzymes, angiotensin converting enzyme (ACE) and chymase might contribute to the development of adriamycin-induced cardiomyopathy in hamsters. Hamsters were administered adriamycin (2.0 mg/kg per day, i.p.) three times weekly for 2 weeks. In the ACE inhibitor-treated group, the hamsters received lisinopril (20 mg/kg per day, p.o.) for 2 weeks after the last injection of adriamycin. The 4-week mortality rates of the vehicle- and ACE inhibitor-treated hamsters were 44% and 12%, respectively. In comparison to the age-matched hamsters used as the control hamsters, a significant decrease in cardiac function and a significant increase in the ratio of the heart weight to the body weight were observed in the vehicle hamsters. Cardiac ACE activity, but not the chymase activity, in the vehicle hamsters was significantly increased in comparison to that in the control hamsters. In the ACE inhibitor-treated group, the increased ACE activity was reduced significantly, and the cardiac hypertrophy and dysfunction were improved significantly. In adriamycin-induced cardiomyopathic hamsters, cardiac ACE activity was increased and ACE inhibition significantly improved cardiac function and survival rate, indicating that cardiac ACE, but not the chymase, plays the pivotal role in the development of the adriamycin-induced cardiomyopathy.
Okumura
Kenichi
K
Department of Pharmacology, Osaka Medical College, Takatsuki City, Japan.
Jin
Denan
D
Takai
Shinji
S
Miyazaki
Mizuo
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D053818:Chymases; D006224:Cricetinae; D004317:Doxorubicin / Q000494:pharmacology*; D004347:Drug Interactions; D006331:Heart Diseases / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D017706:Lisinopril / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009929:Organ Size / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D015996:Survival Rate
D000806:Angiotensin-Converting Enzyme Inhibitors; D004317:Doxorubicin; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; D053818:Chymases