title: Role of endothelin ETB receptor in partial ablation-induced chronic renal failure in rats.
abstract: We investigated the role of endothelin ET(B) receptor in the remnant kidney model of chronic renal failure, by using the spotting-lethal (sl) rat, which carries a naturally occurring deletion in the endothelin ET(B) receptor gene. After 5/6 nephrectomy, systolic blood pressure and renal functional parameters were measured for 12 weeks. At the end of the experimental period, arterial blood sample, remnant kidney, heart and aorta were collected and used for biochemical measurements and histopathological studies. The ET(B)-deficient sl/sl rats exhibited earlier and higher increases in systolic blood pressure, urinary protein excretion, blood urea nitrogen and plasma creatinine concentration, compared with cases in wild-type rats. Histopathologic examination of the kidney revealed glomerular and tubular lesions, alterations of which were more severe in sl/sl than in wild-type rats. While aortic endothelin-1 contents were increased similarly in both groups, the level of renal endothelin-1 content was significantly elevated in sl/sl rats, but not in the wild-type rats. These results suggest that enhanced endothelin-1 production is at least partly responsible for the increased susceptibility to partial ablation-induced chronic renal failure in ET(B) receptor-deficient rats and that ET(B) receptor-mediated actions are protective against vascular and renal injuries in this disease.
authors.affiliation: Department of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Okada
authors.forename: Mariko
authors.initials: M
authors.lastname: Nakata
authors.forename: Hiromi
authors.initials: H
authors.lastname: Izumoto
authors.forename: Mai
authors.initials: M
authors.lastname: Takasu
authors.forename: Naoko
authors.initials: N
authors.lastname: Tazawa
authors.forename: Masanori
authors.initials: M
authors.lastname: Takaoka
authors.forename: Cheryl E
authors.initials: CE
authors.lastname: Gariepy
authors.forename: Masashi
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Matsumura
mesh_terms: D000818:Animals; D017115:Catheter Ablation / Q000379:methods*; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D044023:Receptor, Endothelin B