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(Hypertension. 2002;39:57.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Cardiac and Renal Effects of Growth Hormone in Volume Overload–Induced Heart Failure

Role of NO

Ines Pagel; Thomas Langenickel; Klaus Höhnel; Sebastian Philipp; Andreas K. Nüssler; Werner F. Blum; Michel L. Aubert; Rainer Dietz; Roland Willenbrock

From the Franz-Volhard-Klinik at the Max-Delbrück-Center of Molecular Medicine, Charité (I.P., T.L., K.H., S.P., R.D., R.W.), and the Department of General Surgery, Charité Campus Virchow (A.K.N.), Humboldt-University Berlin, Berlin, Germany; the University Childrens Hospital, Giessen and Lilly Deutschland GmbH (W.F.B.), Bad Homburg, Germany; and the Department of Pediatrics, University of Geneva, School of Medicine (M.L.A.), Geneva, Switzerland.

Correspondence to Roland Willenbrock, MD, Laboratory of Clinical and Experimental Heart Failure (LEH), Franz-Volhard-Klinik, Wiltbergstr. 50, 13125 Berlin, Germany. E-mail willenbrock{at}fvk-berlin.de

Growth hormone (GH) application is a new strategy in the treatment of heart failure. However, clinical and experimental investigations have shown contradictory effects of GH on cardiac performance. We tested the hypothesis that GH could improve cardiac and renal function in volume overload–induced heart failure. The effect of 4 weeks of GH treatment (2 mg/kg daily) was investigated in Wistar rats with aortocaval shunt. GH application did not influence left ventricular contractility and end-diastolic pressure in rats with aortocaval shunt. In contrast, GH treatment normalized impaired diuresis (vehicle 10.8±0.6 mL/d, GH 15.8±0.7 mL/d; P<0.05) and sodium excretion (vehicle 1.5±0.1 mmol/d, GH 2.2±0.1 mmol/d; P<0.001) in shunt-operated rats, with a similar increase of fractional sodium excretion. The urinary excretion of cGMP, the second messenger of atrial natriuretic peptide and NO, was higher in animals with shunts than in sham-operated animals and was further increased by GH (vehicle 293±38 nmol/d, GH 463±57 nmol/d; P<0.01). Although the atrial natriuretic peptide plasma levels were unchanged after GH, the excretion of NO metabolites (nitrate/nitrite) was elevated (vehicle 2020±264 nmol/d, GH 2993±375 nmol/d; P<0.05) in parallel with increased renal mRNA levels of inducible NO synthase 2. The changes of renal function after GH and the increased excretion of NO metabolites and cGMP were abolished by simultaneous treatment with the NO synthase inhibitor N^G-nitro-L-arginine methyl ester. GH treatment did not influence cardiac function in rats with aortocaval shunts. However, GH improved renal function by increasing diuresis and sodium excretion. The responsible mechanism might be the enhanced activity of the renal NO system.

Key Words: heart failure • growth substances • kidney • nitric oxide • nitric oxide synthase • cyclic GMP

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