Böger R H
Institute of Clinical Pharmacology, Medical School, Hannover, Germany.
J Endocrinol Invest. 1999;22(5 Suppl):75-81.
Two major cardiovascular effects of growth hormone (GH) are peripheral vasodilation and increased myocyte growth. Many of the effects of GH on the vascular system are mediated by insulin-like growth factor (IGF)-I. There is abundant evidence that IGF-I stimulates endothelial nitric oxide (NO) synthesis and thereby induces endothelium-dependent vasodilation in experimental models as well as in humans. NO is synthesized by a family of enzymes named NO synthases (NOS), of which three major isoforms have been isolated, cloned and characterized. In endothelial cells, NOS III is a constitutively expressed isoform of NOS which releases small amounts of NO in a calcium-dependent manner. Endothelium-derived NO is an important vasodilator, inhibitor of platelet adhesion and aggregation, inhibitor of monocyte adhesion and inhibitor of vascular smooth muscle cell growth. These pleiotropic cardiovascular actions of NO have been summarized in the characterization of NO as an endogenous antiatherosclerotic molecule. NO-mediated vasodilation is impaired in patients with acquired GH deficiency. Reduced GH-stimulated NO secretion may have important implications in the pathogenesis of heart failure associated with GH deficiency, as it contributes to peripheral vasoconstriction and, thereby, increases afterload. Baseline NO elaboration in patients with adult-onset GH deficiency is reduced compared with that in healthy controls. In GH-deficient patients, chronic substitution of recombinant human GH (rhGH) results in increased rates of synthesis of NO and decreased peripheral arterial resistance. Recent evidence also suggests that GH secretion is reduced in severe heart failure. In addition, GH resistance has been reported in patients with cardiomyopathy, as suggested by an elevated GH/IGF-I ratio. This may contribute to the progression of cardiac failure via a reduction in NO-mediated vasodilation. Clinical studies suggest that NO-mediated vasodilation is impaired in patients with heart failure. Treatment with rhGH may be beneficial in chronic heart failure via a dual action: improved myocardial performance, and peripheral vasodilation mediated via IGF-I/NO/cyclic guanosine monophosphate. This hypothesis deserves further investigation in clinical trials.
生长激素（GH）对心血管系统有两大主要影响，即外周血管舒张和心肌细胞生长增加。GH对血管系统的许多作用是由胰岛素样生长因子（IGF）-I介导的。有充分证据表明，IGF-I可刺激内皮型一氧化氮（NO）合成，从而在实验模型和人类中诱导内皮依赖性血管舒张。NO由一类名为一氧化氮合酶（NOS）的酶合成，已分离、克隆并鉴定出三种主要同工型。在内皮细胞中，NOS III是一种组成型表达的NOS同工型，以钙依赖方式释放少量NO。内皮源性NO是一种重要的血管舒张剂、血小板黏附和聚集抑制剂、单核细胞黏附抑制剂以及血管平滑肌细胞生长抑制剂。NO的这些多效性心血管作用已被总结为将NO表征为一种内源性抗动脉粥样硬化分子。获得性GH缺乏患者的NO介导的血管舒张受损。GH刺激的NO分泌减少可能在与GH缺乏相关的心力衰竭发病机制中具有重要意义，因为它会导致外周血管收缩，从而增加后负荷。与健康对照组相比，成年期起病的GH缺乏患者的基线NO生成减少。在GH缺乏患者中，重组人生长激素（rhGH）的长期替代可导致NO合成速率增加和外周动脉阻力降低。最近的证据还表明，严重心力衰竭患者的GH分泌减少。此外，有报道称心肌病患者存在GH抵抗，表现为GH/IGF-I比值升高。这可能通过减少NO介导的血管舒张而导致心力衰竭进展。临床研究表明，心力衰竭患者的NO介导的血管舒张受损。rhGH治疗可能通过双重作用对慢性心力衰竭有益：改善心肌功能，以及通过IGF-I/NO/环磷酸鸟苷介导外周血管舒张。这一假说值得在临床试验中进一步研究。
