Role of nitric oxide in the vasodilator effect of recombinant human growth hormone in patients with dilated cardiomyopathy.
OBJECTIVE
Dilated cardiomyopathy is characterized by elevated arterial vascular resistance and impaired nitric oxide (NO)-dependent vasodilation. Insulin-like growth factor-I (IGF-I) has been shown to stimulate endothelial NO-synthase resulting in endothelium-dependent vasodilation. Growth hormone (GH) substitution therapy leads in GH-deficient patients to significant increases of IGF-I which may alter systemic vascular resistance by stimulating NO production. This study was designed to evaluate the effects of treatment with recombinant human growth hormone (GH) on NO production and NO-dependent vascular effects in patients with dilated cardiomyopathy.


METHODS
50 patients with dilated cardiomyopathy were randomly assigned to double-blind treatment with 2 I.U. of GH or placebo for 3 months. Central hemodynamics were determined by Swan-Ganz catheter and cardiac output was obtained by the thermodilution method. Serum GH and IGF-I levels were measured and systemic NO production was determined from urinary nitrate and cyclic GMP excretion rates in 42 patients.


RESULTS
GH treatment caused in comparison to the placebo group a significant increase of IGF-I by 91 ng/ml (P = 0.0001). Urinary excretion rates of nitrate and cyclic GMP increased also significantly by 38 mumol/mmol creatinine (P = 0.027) and 65 nmol/mmol creatinine (P = 0.003), respectively. The parallel increase of both marker molecules indicates increased systemic NO production during GH treatment.


CONCLUSIONS
GH treatment induces a significant, but moderate increase of systemic NO production in patients with dilated cardiomyopathy. This effect may be mediated by IGF-I stimulating endothelial NO synthase.
Osterziel
K J
KJ
Charité/Franz-Volhard-Klinik, Humboldt Universität Berlin, Germany. osterziel@fvk-berlin.de
Bode-Böger
S M
SM
Strohm
O
O
Ellmer
A E
AE
Bit-Avragim
N
N
Hänlein
D
D
Ranke
M B
MB
Dietz
R
R
Böger
R H
RH
D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000378:metabolism; D016009:Chi-Square Distribution; D006152:Cyclic GMP / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000502:physiology*; D012044:Regression Analysis
D009566:Nitrates; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D006152:Cyclic GMP