Regulation of insulin-like growth factor-1 by the renin-angiotensin system during regression of cardiac eccentric hypertrophy through angiotensin-converting enzyme inhibitor and AT1 antagonist.
Angiotensin II (Ang II) mediates its effects through its non-tyrosine-kinase G protein coupled Ang-II type 1 receptor (AT1). Growing evidence indicates that a functional insulin-like growth factor-1 (IGF-1) tyrosine kinase receptor is required for Ang-II-induced mitogenesis. Along with Ang II, we have previously shown that changes in IGF-1 receptor binding at myofibers are causative agents for cardiac eccentric hypertrophy. This study investigated the interaction of the renin-angiotensin system with the IGF-1 receptor during the development and regression of cardiac hypertrophy. Alterations in IGF-1 binding were evaluated in the CHAPS-pretreated perfused heart. Four weeks of aortocaval shunt increased relative heart mass by 76% without a major change in body mass or systolic blood pressure. Binding studies showed that IGF-1 has a higher affinity for the cardiac myofibers of shunt than sham rats. Two weeks of treatment with the angiotensin-converting enzyme (ACE) inhibitor captopril (0.5 g/L in drinking water) or the AT1-antagonist losartan (10 mg/(kg x day)) reduced cardiac hypertrophy by 54 and 42%, respectively. However, while both ACE inhibition and AT1-antagonist treatments produced equivalent regression in ventricular hypertrophy, captopril was more efficacious than losartan in the regression of atrial hypertrophy. Regression of cardiac hypertrophy in the shunt by either captopril or losartan was accompanied with a reduction or normalization of the elevated IGF-1 affinity. Thus, the induction and regression of cardiac eccentric hypertrophy seems to be largely dependent on cross talk between the renin-angiotensin system and the IGF-1 axis at the receptor level.
Haddad
G E
GE
Department of Physiology and Biophysics, Howard University, Washington, DC 20059, USA. ghaddad@howard.edu
Blackwell
K
K
Bikhazi
A
A
D000803:Angiotensin I / Q000037:antagonists & inhibitors*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D006348:Cardiac Surgical Procedures; D006332:Cardiomegaly / Q000503:physiopathology*; D004195:Disease Models, Animal; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008297:Male; D008962:Models, Theoretical; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology*; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D007334:Insulin-Like Growth Factor I; D000803:Angiotensin I