Biochemical and Biophysical Research Communications
Ghrelin improves endothelial dysfunction through growth hormone-independent mechanisms in rats
Section snippets
Methods
Experimental animals. Male spontaneous dwarf rats (GH-deficient rats) and male Sprague–Dawley (SD) rats were used in this study. All experimental protocols for animal research were approved by the local authorities of Hiroshima, Japan. At the age of 10 weeks, GH-deficient rats were randomized to receive administration of ghrelin (n=7) or saline (n=7) for three weeks. Similarly, normal rats (SD rats) received placebo for three weeks (n=7). Changes in body weight by treatment with ghrelin or
Effects of ghrelin on body weight, heart rate, and blood pressure
Baseline body weight in GH-deficient rats was significantly lower than that in normal rats (Table 1). GH-deficient rats given placebo showed an impaired increase in body weight compared with normal rats. However, GH-deficient rats treated with ghrelin showed a significantly greater increase in body weight than those given placebo. Heart rate and blood pressure tended to decrease in GH-deficient rats treated with ghrelin, although these changes did not reach statistical significance.
Effect of ghrelin on aortic vasorelaxation
After
Discussion
This is the first study to demonstrate beneficial effects of ghrelin on endothelial function in rats. In the present study, we demonstrated that (1) three-week administration of ghrelin improved impaired endothelium-dependent vasorelaxation in GH-deficient rats, (2) ACh-induced vasorelaxation was inhibited by l-NAME, but not by indomethacin, and (3) ghrelin increased expression of eNOS protein in the aorta of GH-deficient rats.
GHS-R, a specific receptor for ghrelin, exists not only in the
Acknowledgements
This work was supported by the Promotion of Fundamental Studies in Health Science of the Organization for Pharmaceutical Safety and Research (OPSR) of Japan.
References (33)
Endothelial function as a determinant of vascular function and structure: a new therapeutic target
Am. J. Cardiol.
(1997)- et al.
Nitric oxide and its role in the cardiovascular system
Prog. Cardiovasc. Dis.
(1995) - et al.
Central effects of a novel acylated peptide, ghrelin, on growth hormone release in rats
Biochem. Biophys. Res. Commun.
(2000) - et al.
Impaired endothelium-mediated vasodilation in the peripheral vasculature of patients with congestive heart failure
J. Am. Coll. Cardiol.
(1992) - et al.
Identification of flow-dependent endothelial nitric-oxide synthase phosphorylation sites by mass spectrometry and regulation of phosphorylation and nitric oxide production by the phosphatidylinositol 3-kinase inhibitor LY294002
J. Biol. Chem.
(1999) - et al.
Up-regulation of endothelial nitric oxide synthase through beta(2)-adrenergic receptor—the role of a beta-blocker with NO-releasing action
Biochem. Biophys. Res. Commun.
(2001) - et al.
Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries
N. Engl. J. Med.
(1986) The endothelium-modulator of vascular smooth-muscle tone
N. Engl. J. Med.
(1988)- et al.
Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells
J. Clin. Invest.
(1989) - et al.
Nitric oxide: physiology, pathophysiology, and pharmacology
Pharmacol. Rev.
(1991)
Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines
J. Clin. Invest.
Endothelial control of the cardiovascular system: recent advances
FASEB J.
Molecular cloning and characterization of the constitutive bovine aortic endothelial cell nitric oxide synthase
J. Clin. Invest.
Nitric oxide in the pathogenesis of vascular disease
J. Pathol.
Ghrelin is a growth-hormone-releasing acylated peptide from stomach
Nature
Ghrelin strongly stimulates growth hormone release in humans
J. Clin. Endocrinol. Metab.
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