title: Enhanced intrarenal receptor-mediated prorenin activation in chronic progressive anti-thymocyte serum nephritis rats on high salt intake.
abstract: Despite suppression of the circulating renin-angiotensin system (RAS), high salt intake (HSI) aggravates kidney injury in chronic kidney disease. To elucidate the effect of HSI on intrarenal RAS, we investigated the levels of intrarenal prorenin, renin, (pro)renin receptor (PRR), receptor-mediated prorenin activation, and ANG II in chronic anti-thymocyte serum (ATS) nephritic rats on HSI. Kidney fibrosis grew more severe in the nephritic rats on HSI than normal salt intake. Despite suppression of plasma renin and ANG II, marked increases in tubular prorenin and renin proteins without concomitant rises in renin mRNA, non-proteolytically activated prorenin, and ANG II were noted in the nephritic rats on HSI. Redistribution of PRR from the cytoplasm to the apical membrane, along with elevated non-proteolytically activated prorenin and ANG II, was observed in the collecting ducts and connecting tubules in the nephritic rats on HSI. Olmesartan decreased cortical prorenin, non-proteolytically activated prorenin and ANG II, and apical membranous PRR in the collecting ducts and connecting tubules, and attenuated the renal lesions. Cell surface trafficking of PRR was enhanced by ANG II and was suppressed by olmesartan in Madin-Darby canine kidney cells. These data suggest the involvement of the ANG II-dependent increase in apical membrane PRR in the augmentation of intrarenal binding of prorenin and renin, followed by nonproteolytic activation of prorenin, enhancement of renin catalytic activity, ANG II generation, and progression of kidney fibrosis in the nephritic rat kidneys on HSI. The origin of the increased tubular prorenin and renin remains to be clarified. Further studies measuring the urinary prorenin and renin are needed.
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Japan. huangyanjie69@hotmail.com
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Huang
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Taro
authors.initials: T
authors.lastname: Misaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Akashi
authors.initials: A
authors.lastname: Togawa
authors.forename: Naro
authors.initials: N
authors.lastname: Ohashi
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Fukasawa
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujigaki
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Ichihara
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Takaaki
authors.initials: T
authors.lastname: Senbonmatsu
authors.forename: Naoki
authors.initials: N
authors.lastname: Ikegaya
authors.forename: Akira
authors.initials: A
authors.lastname: Hishida
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000961:Antilymphocyte Serum / Q000276:immunology* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006830:Hydralazine / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009393:Nephritis / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012083:Renin / Q000378:metabolism*; D017673:Sodium Chloride, Dietary; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology; D000093342:Prorenin Receptor
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D000961:Antilymphocyte Serum; D007093:Imidazoles; D011956:Receptors, Cell Surface; D017673:Sodium Chloride, Dietary; D013777:Tetrazoles; D000804:Angiotensin II; D006830:Hydralazine; C437965:olmesartan; D012083:Renin; D000093342:Prorenin Receptor