Differential Cardiac Effects of Growth Hormone and Insulin-like Growth Factor1 in the Rat

BACKGROUND: Despite their increasing clinical use and recent evidence that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) target the heart, there has been no systematic investigation of the effects of GH and IGF-1 on the cardiovascular system. METHODS AND RESULTS: Sixty normal but growing adult female rats were randomized to receive 4 weeks of treatment with GH (3.5 mg.kg-1.d-1), IGF-1 (3 mg.kg-1.d-1), a combination of the two, or placebo. Transthoracic echocardiograms were performed at baseline and at 2 weeks and 4 weeks of treatment. After the final echocardiography, rats underwent either closed-chest left ventricular (LV) catheterization or Langendorff perfusion studies. Myocyte diameter and interstitial tissue fraction were assessed by morphometric histology. Echocardiographic and ex vivo data demonstrated a LV hypertrophic response in all three groups of treated animals that was most marked in the GH group, which alone exhibited a concentric growth pattern (relative wall thickness, 0.52 versus 0.42 to 0.44 in the other groups; P < .001). At 4 weeks, cardiac index was significantly higher and total systemic vascular resistance was lower in all groups of treated animals than in control animals (both P < .001), whereas arterial blood pressure did not differ significantly. All indexes of in vivo and in vitro cardiac function were higher in GH- and IGF-1-treated rats than in control animals, whereas combination therapy yielded a blunted effect. Myocyte diameter was increased in all three treated groups without an increase in interstitial tissue. CONCLUSIONS: Exogenous administration of GH and IGF-1 in the normal adult rat induces a cardiac hypertrophic response without development of significant fibrosis. Cardiac performance is increased both in vivo and in the isolated heart.