title: Cardiac and renal effects of growth hormone in volume overload-induced heart failure: role of NO.
abstract: 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.
authors.affiliation: Franz-Volhard-Klinik at the Max-Delbrück-Center of Molecular Medicine, Charité, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Pagel
authors.forename: Thomas
authors.initials: T
authors.lastname: Langenickel
authors.forename: Klaus
authors.initials: K
authors.lastname: Höhnel
authors.forename: Sebastian
authors.initials: S
authors.lastname: Philipp
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Nüssler
authors.forename: Werner F
authors.initials: WF
authors.lastname: Blum
authors.forename: Michel L
authors.initials: ML
authors.lastname: Aubert
authors.forename: Rainer
authors.initials: R
authors.lastname: Dietz
authors.forename: Roland
authors.initials: R
authors.lastname: Willenbrock
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D006152:Cyclic GMP / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D013006:Growth Hormone / Q000097:blood; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D009929:Organ Size; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy
chemical_list: D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000804:Angiotensin II; D019382:Human Growth Hormone; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D009320:Atrial Natriuretic Factor; D013006:Growth Hormone; C496320:NOS1 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496316:Nos3 protein, rat; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester