title: Renal medullary (pro)renin receptor contributes to angiotensin II-induced hypertension in rats via activation of the local renin-angiotensin system.
abstract: BACKGROUND
  (Pro)renin receptor (PRR) is a new component of the renin-angiotensin system and regulates renin activity in vitro. Within the kidney, PRR is highly expressed in the renal medulla where its expression is induced by angiotensin II infusion. The objective of the present study was to test a potential role of renal medullary PRR during angiotensin II-induced hypertension.
  
  
  METHODS
  A rat AngII infusion model (100 ng/kg/min) combined with renal intramedullary infusion of PRO20, a specific inhibitor of PRR, was builded. And the intravenous PRO20 infusion serve as control. Mean arterial pressure was recorded by radiotelemetry for one week. Further analysis of kidney injury, inflammation, biochemical indices and protein localization were performed in vivo or in vitro.
  
  
  RESULTS
  Radiotelemetry demonstrated that AngII infusion elevated the mean arteria pressure from 108 ± 5.8 to 164.7 ± 6.2 mmHg. Mean arterial pressure decreased to 128.6 ± 5.8 mmHg (P < 0.05) after intramedullary infusion of PRO20, but was only modestly affected by intravenous PRO20 infusion. Indices of kidney injury, including proteinuria, glomerulosclerosis, and interstitial fibrosis, inflammation, and increased renal medullary and urinary renin activity following angiotensin II infusion were all remarkably attenuated by intramedullary PRO20 infusion. Following one week of angiotensin II infusion, increased PRR immunoreactivity was found in vascular smooth muscle cells. In cultured rat vascular smooth muscle cells, angiotensin II induced parallel increases in soluble PRR and renin activity, and the latter was significantly reduced by PRO20.
  
  
  CONCLUSIONS
  Renal medullary PRR mediates angiotensin II-induced hypertension, likely by amplifying the local renin response.
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, #74 Zhongshan 2nd Road, Science and Technology Building, 6th Floor, Guangzhou, 510080, P. R. China.|Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, UT, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, #74 Zhongshan 2nd Road, Science and Technology Building, 6th Floor, Guangzhou, 510080, P. R. China.
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Lu
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, #74 Zhongshan 2nd Road, Science and Technology Building, 6th Floor, Guangzhou, 510080, P. R. China.
authors.forename: Mi
authors.initials: M
authors.lastname: Liu
authors.affiliation: Departments of Pharmacology and Physiology & Cell Biology, University of Nevada School of Medicine, Reno, NE, USA.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA.
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Zhou
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, #74 Zhongshan 2nd Road, Science and Technology Building, 6th Floor, Guangzhou, 510080, P. R. China. Yangtxin@mail.sysu.edu.cn.|Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, UT, USA. Yangtxin@mail.sysu.edu.cn.
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yang
mesh_terms: D000804:Angiotensin II / Q000009:adverse effects*; D000818:Animals; D006973:Hypertension / Q000139:chemically induced*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface; D012083:Renin / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D011956:Receptors, Cell Surface; D000804:Angiotensin II; D012083:Renin