Potential contribution of endothelin to renal abnormalities in glycerol-induced acute renal failure in rats.
We studied the possible participation of endothelin-1 (ET-1) in the pathogenesis of renal damage in glycerol-induced acute renal failure (ARF). Cortical mRNA expression of ET-1 increased, peaking at 10 hr postinjury, but this did not occur in the medulla, plasma concentration and urinary excretion of ET-1 also increased in this model. There was no change in ETA receptor mRNA, whereas the ETB receptor tended to be down-regulated in the kidney after glycerol administration. In situ hybridization study demonstrated that elevated expression of prepro ET-1 was predominantly localized in cells in the proximal tubules of the nephritic kidney. The administration (30-3 mg/kg) of S-0139, (+)-disodium 27-[(E)-3-[2-[(E)-3-carboxylatoacryloylamino]-5-hydroxyphenl ]acrylayl oxy]-3-oxoolean-12-en-28-oate, an ETA selective antagonist, after initiation of insult offered dose-dependent prevention against ARF, demonstrating preventing of renal function impairment and mortality. These findings indicate that ET-1 participates in the pathogenesis of acute tubular injury in glycerol-induced ARF and that ETA antagonist may be useful in the treatment of some types of human ARF.
Shimizu
T
T
Shionogi Research Laboratories, Shionogi & Co., Ltd., Futaba-cho, Toyonaka, Osaka 561, Japan.
Kuroda
T
T
Ikeda
M
M
Hata
S
S
Fujimoto
M
M
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology*; D000818:Animals; D003404:Creatinine / Q000097:blood / Q000652:urine; D016232:Endothelins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D005990:Glycerol; D006801:Humans; D017403:In Situ Hybridization; D007457:Iodine Radioisotopes; D007668:Kidney / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000096:biosynthesis
D016232:Endothelins; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D003404:Creatinine; D005990:Glycerol