Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency. A double-blind, placebo-controlled study.

Abstract

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-1 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 Ϯ 7.4 mol/ mmol creatinine; cyclic GMP, 63.6 Ϯ 7.1 nmol/mmol creatinine) as compared with healthy controls (nitrate, 167.3 Ϯ 7.5 mol/mmol creatinine; cyclic GMP, 155.2 Ϯ 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 ‫ف‬ 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

The prolactin family hormones regulate vascular tone through NO and prostacyclin production in isolated rat aortic rings

“…In contrast to the findings described above, both in vitro [26] and in vivo studies [27,28] indicate that GH induces eNOSmediated NO production. In the human endothelial cell line, EAht926, high concentrations of GH regulate eNOS expression and NO production [26] , effects that also occur in human aortic endothelial cells [29] .…”

“…In the human endothelial cell line, EAht926, high concentrations of GH regulate eNOS expression and NO production [26] , effects that also occur in human aortic endothelial cells [29] . Based on these findings, the loss of GH in humans decreases both blood flow and NO levels, whereas GH replacement restores these vascular responses [27,30,31] , indicating that patients with GH deficiency are at increased cardiovascular risk [32] .…”

Influence of ghrelin gene polymorphisms on hypertension and atherosclerotic disease

“…This variant has been shown to be associated with decreased IGF-1 concentrations, and IGF-1 has been shown to stimulate endothelial nitric oxide formation. 18 Such observations might explain the association of rs34911341 with hypertension. 11 In single-locus analysis, no other studied SNP was associated with hypertension or blood pressure.…”

GH and IGF-I regulate the expression of endothelial nitric oxide synthase (eNOS) in cardiovascular tissues of hypophysectomized female rats

“…These patients demonstrate normal blood pressure, hypotension or hypertension (for review see (2)). They also have endothelial dysfunction (3) and decreased nitric oxide (NO) formation (4). Several studies have shown the clinical benefits of GH therapy on cardiovascular function in these patients, such as unchanged or decreased systolic and diastolic blood pressure (BP), increased cardiac output (CO), increased heart rate (HR) (4,5), increased NO formation (4) and decreased vascular resistance (5).…”