Overexpression of insulin-like growth factor-I in hearts of rats with isoproterenol-induced cardiac hypertrophy.

Increased levels of plasma catecholamine lead to cardiac hypertrophy via the alpha-, beta-adrenergic receptors, and partially, type 1 angiotensin II (AT1) receptor. However, it remains unclear whether other factors are involved in catecholamine-induced cardiac hypertrophy. We investigated the expression of insulin-like growth factor (IGF)-I in hearts of male Wistar rats infused with a beta-adrenergic agent, isoproterenol (ISO) (3 mg/kg/day), with or without an AT1-receptor antagonist, TCV-116 (10 mg/kg/day). Cardiac myocytes became hypertrophied 1 day after the beginning of ISO administration. ISO induced a biphasic increase of cardiac myocytes positive for IGF-I protein in the early and late phases of the study period, whereas IGF-I gene expression was upregulated only in the late phase by ISO. TCV- 116 abolished the upregulation of IGF-I gene and protein expression in the late phase in association with the regression of cardiac hypertrophy. These results suggest that ISO-induced cardiac hypertrophy is mediated, at least in part, by IGF-I, the expression of which is upregulated through the activation of AT1 receptor.