Ghrelin improves endothelial dysfunction through growth hormone-independent mechanisms in rats.
Ghrelin is a novel growth hormone (GH)-releasing peptide which was isolated from the stomach. We have reported that ghrelin causes vasorelaxation in rats through GH-independent mechanisms. We investigated whether ghrelin improves endothelial dysfunction. Ghrelin was subcutaneously administered to GH-deficient rats for three weeks. After isolation of the thoracic aorta, aortic ring tension was measured to evaluate vasorelaxation. Acetylcholine-induced vasorelaxation was impaired in GH-deficient rats given placebo compared to that in normal rats given placebo. GH-deficient rats treated with ghrelin, however, showed a significant increase in the maximal relaxation as compared with those given placebo. This improvement by ghrelin was inhibited by N(G)-nitro-L-arginine methyl ester, a nonselective nitric oxide synthase (NOS) inhibitor. Western blot analysis demonstrated that treatment with ghrelin increased endothelial NOS (eNOS) expression in the aorta of GH-deficient rats. These results suggest that administration of ghrelin improves endothelial dysfunction and increases eNOS expression in rats through GH-independent mechanisms.
Shimizu
Yoshito
Y
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Nagaya
Noritoshi
N
Teranishi
Yasuhiro
Y
Imazu
Michinori
M
Yamamoto
Hideya
H
Shokawa
Tomoki
T
Kangawa
Kenji
K
Kohno
Nobuoki
N
Yoshizumi
Masao
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001161:Arteriosclerosis / Q000188:drug therapy; D001794:Blood Pressure; D015153:Blotting, Western; D001835:Body Weight; D002317:Cardiovascular Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054439:Ghrelin; D013006:Growth Hormone / Q000378:metabolism*; D006339:Heart Rate; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D036361:Peptide Hormones / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D010919:Placebos; D051381:Rats; D017207:Rats, Sprague-Dawley
D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D054439:Ghrelin; D036361:Peptide Hormones; D010919:Placebos; D009599:Nitroprusside; D013006:Growth Hormone; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin