Pagel Ines, Langenickel Thomas, Höhnel Klaus, Philipp Sebastian, Nüssler Andreas K, Blum Werner F, Aubert Michel L, Dietz Rainer, Willenbrock Roland
Franz-Volhard-Klinik at the Max-Delbrück-Center of Molecular Medicine, Charité, Germany.
Hypertension. 2002 Jan;39(1):57-62. doi: 10.1161/hy0102.098323.
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.
生长激素（GH）应用是治疗心力衰竭的一种新策略。然而，临床和实验研究表明GH对心脏功能有相互矛盾的影响。我们检验了GH可改善容量超负荷诱导的心力衰竭患者心脏和肾功能的假设。研究了对Wistar大鼠进行4周GH治疗（每日2mg/kg）对主动脉腔静脉分流术的影响。GH应用对主动脉腔静脉分流大鼠的左心室收缩力和舒张末期压力没有影响。相反，GH治疗使分流手术大鼠受损的利尿功能（载体组10.8±0.6mL/d，GH组15.8±0.7mL/d；P<0.05）和钠排泄（载体组1.5±0.1mmol/d，GH组2.2±0.1mmol/d；P<0.001）恢复正常，钠排泄分数有类似增加。心房利钠肽和一氧化氮的第二信使cGMP的尿排泄量在分流动物中高于假手术动物，并且GH使其进一步增加（载体组293±38nmol/d，GH组463±57nmol/d；P<0.01）。尽管GH治疗后心房利钠肽血浆水平未改变，但一氧化氮代谢产物（硝酸盐/亚硝酸盐）的排泄增加（载体组2020±264nmol/d，GH组2993±375nmol/d；P<0.05），同时肾脏中诱导型一氧化氮合酶2的mRNA水平升高。GH治疗后肾功能的变化以及一氧化氮代谢产物和cGMP排泄的增加被一氧化氮合酶抑制剂N(G)-硝基-L-精氨酸甲酯同时治疗所消除。GH治疗对主动脉腔静脉分流大鼠的心脏功能没有影响。然而，GH通过增加利尿和钠排泄改善了肾功能。其相关机制可能是肾脏一氧化氮系统活性增强。
