title: Ghrelin improves renal function in mice with ischemic acute renal failure.
abstract: Growth hormone and IGF-1 have been suggested to have tissue-protective effects. Ghrelin is a stomach-derived growth hormone secretagogue. The effects of ghrelin on ischemia/reperfusion-induced renal failure in mice were examined. Ischemic acute renal failure was induced by bilateral renal artery clamping for 45 min and reperfusion for 24 h. Ghrelin (100 microg/kg mouse) or vehicle was injected subcutaneously six times before surgery and three times after surgery every 8 h. Twenty-four hours after reperfusion, the right kidney was isolated and perfused. Acetylcholine (ACh)- and adrenomedullin-induced endothelium-dependent vasorelaxation of renal vessels significantly improved in ghrelin-pretreated mice (%Delta renal perfusion pressure by 10(-7) M ACh -63.5 +/- 3.7 versus -41.2 +/- 5.5%; P < 0.05). This change was associated with significant increases of nitric oxide release in the kidneys of ghrelin-treated mice (10(-7) M ACh 35.5 +/- 5.8 versus 16.9 +/- 3.5 fmol/g kidney per min; P < 0.05). Serum concentration of urea nitrogen (53 +/- 7 versus 87 +/- 15 mg/dl; P < 0.05) and renal injury score were significantly lower in the ghrelin group (2.5 +/- 0.8 versus 5.3 +/- 1.5; P < 0.01). Tubular apoptotic index was significantly lower in the ghrelin group (5 +/- 5 versus 28 +/- 4; P < 0.05). Furthermore, the survival rate after the 60-min ischemic period was higher in the ghrelin group (80 versus 20%; P < 0.05). Ghrelin treatment significantly increased the serum level of IGF-1. However, such renal protective effects of ghrelin on ischemia/reperfusion injury were not observed in insulin receptor substrate-2 knockout mice. These results suggest that ghrelin may protect the kidneys from ischemia/reperfusion injury and that this effect is related to an improvement of endothelial function through an IGF-1-mediated pathway.
authors.affiliation: Department of Cardiovascular Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Takeda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nishimatsu
authors.forename: Etsu
authors.initials: E
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Satonaka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nagata
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Oba
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
authors.forename: Masao
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.forename: Tadaichi
authors.initials: T
authors.lastname: Kitamura
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hirata
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D054439:Ghrelin; D055504:Insulin Receptor Substrate Proteins; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney / Q000098:blood supply* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000502:physiology; D036361:Peptide Hormones / Q000494:pharmacology / Q000627:therapeutic use*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology; D015427:Reperfusion Injury / Q000517:prevention & control*; D015996:Survival Rate
chemical_list: D054439:Ghrelin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526298:Irs2 protein, mouse; D036361:Peptide Hormones; D010750:Phosphoproteins; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases