Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency - A double-blind, placebo-controlled study
Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency - A double-blind, placebo-controlled study
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DOI：
10.1172/jci119095
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发表时间：
1996-12-15
影响因子：
15.9
通讯作者：
Frolich, JC
中科院分区：
文献类型：
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作者：
Boger, RH;Skamira, C;Frolich, JC
我们在一项双盲、安慰剂对照的试验中研究了重组生长激素对获得性生长激素缺乏症成人患者全身一氧化氮（NO）形成和血流动力学的影响。将30例患者随机分配至重组人生长激素（r-hGH; 2.0 IU/d）或安慰剂组，治疗12个月。在随后的12个月，研究继续与两组患者接受r-hGH。在每年的第1，3，6，9，和12个月，尿液和血浆样品收集用于测定尿硝酸盐和环GMP作为指标的全身NO生产，和血浆IGF-I水平。在治疗的第1个月，12个月和24个月通过超声心动图测量心输出量。r-hGH在治疗的第一个月内诱导血浆IGF-1浓度增加4倍，生长激素缺乏患者的尿硝酸盐和环GMP排泄率在基线时较低（硝酸盐，96.8+/-7.4 μ mol/mmol肌酐，环GMP，63.6+/-7.1 nmol/mmol肌酐）与健康对照组相比（硝酸盐，167.3+/-7.5 μ mol/mmol肌酐;环GMP，155.2+/-6.9 nmol/mmol肌酐）。在GH组的第一个12个月内，以及在安慰剂组的第二个12个月内，r-hGH显著增加了NO产生的这些指数。虽然收缩压和舒张压未被r-hGH显著改变，但当被分配至r-hGH治疗时，两组的心输出量显著增加30- 40%，总外周阻力降低30%。在第二个研究年，当两组都给予r-hGH时，血浆IGF-1没有显著差异。尿硝酸盐，或环GMP排泄，或两组之间的血液动力学参数。总之，全身NO的形成减少在未经治疗的生长激素缺乏症患者。用重组人生长激素治疗使尿硝酸盐和环GMP排泄正常化，可能是通过IGF-1刺激内皮NO形成，并伴随降低外周动脉阻力。增加NO的形成可能是生长激素治疗期间获得性垂体功能减退患者心血管功能改善的原因之一。
We studied the effects of recombinant growth hormone on systemic nitric oxide (NO) formation and hemodynamics in a double-blind, placebo-controlled trial in adult patients with acquired growth hormone deficiency. 30 patients were randomly allocated to either recombinant human growth hormone (r-hGH; 2.0 IU/d) or placebo for 12 mo. In the subsequent 12 mo, the study was continued with both groups of patients receiving r-hGH.In months 1, 3, 6, 9, and 12 of each year, urine and plasma samples were collected for the determination of urinary nitrate and cyclic GMP as indices of systemic NO production, and of plasma IGF-I levels. Cardiac output was measured in months 1, 12, and 24 by echocardiography.r-hGH induced a fourfold increase in plasma IGF-1 concentrations within the first month of treatment, Urinary nitrate and cyclic GMP excretion rates were low at baseline in growth hormone-deficient patients (nitrate, 96.8+/-7.4 mu mol/mmol creatinine, cyclic GMP, 63.6+/-7.1 nmol/mmol creatinine) as compared with healthy controls (nitrate, 167.3+/-7.5 mu mol/mmol creatinine; cyclic GMP, 155.2+/-6.9 nmol/mmol creatinine). These indices of NO production were significantly increased by r-hGH, within the first 12 mo in the GH group, and within the second 12 mo in the placebo group. While systolic and diastolic blood pressure were not significantly altered by r-hGH, cardiac output significantly increased by 30-40%, and total peripheral resistance decreased by similar to 30% in both groups when they were assigned to r-hGH treatment. In the second study year, when both groups were given r-hGH, there were no significant differences in plasma IGF-1. urinary nitrate, or cyclic GMP excretion, or hemodynamic parameters between both groups.In conclusion, systemic NO formation is decreased in untreated growth hormone-deficient patients. Treatment with recombinant human growth hormone normalizes urinary nitrate and cyclic GMP excretion, possibly via IGF-1 stimulation of endothelial NO formation, and concomitantly decreases peripheral arterial resistance. Increased NO formation may be one reason for improved cardiovascular performance of patients with acquired hypopituitarism during growth hormone therapy.