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.
Suzuki
J
J
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Ohno
I
I
Nawata
J
J
Miura
S
S
Ikeda
J
J
Shirato
K
K
D000318:Adrenergic beta-Agonists / Q000633:toxicity*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D015152:Blotting, Northern; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007545:Isoproterenol / Q000633:toxicity*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles
D000318:Adrenergic beta-Agonists; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D007334:Insulin-Like Growth Factor I; D007545:Isoproterenol; C077793:candesartan cilexetil