Beneficial effects of growth hormone and insulin-like growth factor-1 in experimental heart failure in rats treated with chronic ACE inhibition.
The effects of growth hormone (GH) plus insulin-like growth factor-1 (IGF-1) were tested in an experimental model of cardiac failure treated with chronic angiotensin-converting enzyme (ACE) inhibition. Myocardial infarction was induced in rats by left coronary artery ligation. Two weeks after ligation, the animals received either captopril (2 g/L in drinking water) or water for 3 months. The rats were then given either GH (2 mg/kg/day) plus IGF-1 (2 mg/kg/day) or vehicle for 14 days. Captopril treatment decreased mean arterial pressure (MAP), left ventricular end-diastolic pressure (LVEDP) and systemic vascular resistance (SVR) (p < 0.05), and increased cardiac index (CI) and stroke volume index (SVI) (p < 0.05). GH/IGF-1 or captopril+GH/IGF-1 treatment decreased MAP, LVEDP, and SVR (p < 0.05), and increased left ventricular maximum dP/dt, CI, and SVI (p < 0.05). The increases in CI and SVI were significantly greater in the captopril+GH/IGF-1-treated animals than in those treated with captopril alone (p < 0.05). The beneficial effect of captopril in reducing cardiac hypertrophy was preserved in the captopril+GH/IGF-1 group. The results indicate that GH/IGF-1 and captopril can improve cardiac performance in congestive heart failure by independent and complementary mechanisms.
Jin
H
H
Department of Cardiovascular Research, Genentech, Inc., South San Francisco, California 94080, USA.
Yang
R
R
Gillett
N
N
Clark
R G
RG
Ko
A
A
Paoni
N F
NF
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D013006:Growth Hormone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D002216:Captopril