title: Sequential activation of the intrarenal renin-angiotensin system in the progression of hypertensive nephropathy in Goldblatt rats.
abstract: The intrarenal renin-angiotensin system (RAS) has an important role in generating and maintaining hypertension in two-kidney, one-clip (2K1C) rats. This study evaluated how various intrarenal RAS components contributed to hypertension not only in the maintenance period (5w; 5 wk after operation) but also earlier (2w; 2 wk after operation). We inserted a 2.5-mm clip into the left renal artery of Sprague-Dawley rats and euthanized them at 2w and 5w following the operation. Systolic blood pressure increased within 1 wk after the operation, and left ventricular hypertrophy occurred in 2K1C rats. At 2w, juxtaglomerular apparatus (JGA) and collecting duct (CD) renin increased in clipped kidney (CK) of 2K1C rats. The tubular angiotensin I-converting enzyme (ACE) was not changed, but peritubular ACE2 decreased in nonclipped kidney (NCK) and CK of 2K1C rats. At 5w, ACE and CD renin were enhanced, and ACE2 was still lessened in both kidneys of 2K1C rats. However, plasma renin activity (PRA) was not different from that in sham rats. In proximal tubules of CK, the ANG II type 1 receptor (AT1R) was not suppressed, but the Mas receptor (MasR) was reduced; thus the AT1R/MasR ratio was elevated. Although hypoxic change in CK could not be excluded, the JGA renin of CK and CD renin in both kidneys was highly expressed independent of time. Peritubular ACE2 changed in the earlier period, and uninhibited AT1R in proximal tubules of CK was presented in the maintenance period. In 2K1C rats, attenuated ACE2 seems to contribute to initiating hypertension while upregulated ACE in combination with unsuppressed AT1R may have a key role in maintaining hypertension.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea;
authors.forename: Yang Gyun
authors.initials: YG
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea;
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea;
authors.forename: Se-Yun
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea;
authors.forename: Arah
authors.initials: A
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea;
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Moon
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea;
authors.forename: Kyung-Hwan
authors.initials: KH
authors.lastname: Jeong
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea;
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Lee
authors.affiliation: Department of Pathology, Kyung Hee University College of Medicine, Seoul, Korea; and.
authors.forename: Sung Jig
authors.initials: SJ
authors.lastname: Lim
authors.affiliation: Department of Cardiology, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul, Korea.
authors.forename: Il Suk
authors.initials: IS
authors.lastname: Sohn
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea; cgihm@yahoo.co.kr.
authors.forename: Chun-Gyoo
authors.initials: CG
authors.lastname: Ihm
mesh_terms: D000818:Animals; D001794:Blood Pressure; D018450:Disease Progression; D004452:Echocardiography; D006977:Hypertension, Renal / Q000209:etiology / Q000503:physiopathology*; D006978:Hypertension, Renovascular / Q000150:complications / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000209:etiology; D007606:Juxtaglomerular Apparatus / Q000473:pathology; D007668:Kidney / Q000503:physiopathology*; D007685:Kidney Tubules, Collecting / Q000473:pathology; D008297:Male; D009393:Nephritis / Q000209:etiology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System
keywords: 2-kidney 1-clip rat; ACE; ACE2; intrarenal renin-angiotensin system (RAS)