title: Augmented circadian rhythm of the intrarenal renin-angiotensin systems in anti-thymocyte serum nephritis rats.
abstract: We report that disturbance to the circadian rhythm of urinary angiotensinogen (AGT) excretion may lead to renal damage, hypertension and diurnal blood pressure (BP) variations. We aim to clarify the circadian rhythm of the intrarenal renin-angiotensin system (RAS) and its contribution to renal damage, hypertension and BP variations, and to evaluate whether the administration of RAS blockers influences the circadian rhythms of intrarenal RAS components. Anti-thymocyte serum (ATS) nephritis rats were used as a chronic progressive glomerulonephritis model (group A) and compared with control rats (group C). Other rats with ATS nephritis received olmesartan medoxomil (an angiotensin II (AngII) type 1 receptor (AT1R) blocker; group AO) or hydralazine (a vasodilator; group AH). The levels of intrarenal RAS components were evaluated every 6 h. The expression levels of intrarenal AGT, AngII and AT1R were increased in group A and peaked at the same time as BP and urinary protein excretion during the rest phase. The amplitude of the circadian fluctuation of these proteins was more increased in group A than in group C. The circadian fluctuation of these proteins was reduced in groups AO and AH. However, renal function, proteinuria and augmentation of intrarenal RAS components were reduced only in group AO. Intrarenal RAS components, such as AGT, AngII and AT1R proteins, were increased and the amplitude of the oscillations of these proteins was augmented in ATS nephritis rats. Interestingly, renal damage may be linked to the activation of the intrarenal RAS independent of the amplitude of its oscillations and BP.
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Isobe
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Naro
authors.initials: N
authors.lastname: Ohashi
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Ishigaki
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Blood Purification Unit, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Sakao
authors.affiliation: Blood Purification Unit, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kato
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyajima
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu, Japan.|Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujigaki
authors.affiliation: Department of Pharmacology, Kagawa University, Kagawa, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.affiliation: Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yasuda
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000808:Angiotensinogen / Q000378:metabolism; D000818:Animals; D000961:Antilymphocyte Serum / Q000276:immunology*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D006830:Hydralazine / Q000494:pharmacology / Q000627:therapeutic use; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D009393:Nephritis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D000068557:Olmesartan Medoxomil / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
chemical_list: D000961:Antilymphocyte Serum; D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D000804:Angiotensin II; D006830:Hydralazine; D000068557:Olmesartan Medoxomil