title: COX-2 mediates angiotensin II-induced (pro)renin receptor expression in the rat renal medulla.
abstract: (Pro)renin receptor (PRR) is predominantly expressed in the distal nephron where it is activated by angiotensin II (ANG II), resulting in increased renin activity in the renal medulla thereby amplifying the de novo generation and action of local ANG II. The goal of the present study was to test the role of cycloxygenase-2 (COX-2) in meditating ANG II-induced PRR expression in the renal medulla in vitro and in vivo. Exposure of primary rat inner medullary collecting duct cells to ANG II induced sequential increases in COX-2 and PRR protein expression. When the cells were pretreated with a COX-2 inhibitor NS-398, ANG II-induced upregulation of PRR protein expression was almost completely abolished, in parallel with the changes in medium active renin content. The inhibitory effect of NS-398 on the PRR expression was reversed by adding exogenous PGE2. A 14-day ANG II infusion elevated renal medullary PRR expression and active and total renin content in parallel with increased urinary renin, all of which were remarkably suppressed by the COX-2 inhibitor celecoxib. In contrast, plasma and renal cortical active and total renin content were suppressed by ANG II treatment, an effect that was unaffected by COX-2 inhibition. Systolic blood pressure was elevated with ANG II infusion, which was attenuated by the COX-2 inhibition. Overall, the results obtained from in vitro and in vivo studies established a crucial role of COX-2 in mediating upregulation of renal medullary PRR expression and renin content during ANG II hypertension.
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China; Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah; and.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China; Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah; and.
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Lu
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China; Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah; and.
authors.forename: Kexin
authors.initials: K
authors.lastname: Peng
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China;
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China;
authors.forename: Chunling
authors.initials: C
authors.lastname: Li
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China;
authors.forename: Weidong
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yu
authors.affiliation: Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah; and.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Kohan
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, Florida.
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Zhu
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China; Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah; and Tianxin.Yang@hsc.utah.edu.
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000187:drug effects / Q000378:metabolism*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D000804:Angiotensin II; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D012083:Renin
keywords: (pro)renin receptor; cyclooxygenase-2; inner medullary collecting duct; prostaglandin E2; renin activity
references.citation: Kidney Int. 2007 Aug;72(3):274-8
references.pmid: 17495855
references.citation: Antioxid Redox Signal. 2013 Jan 1;18(1):51-65
references.pmid: 22671943
references.citation: Am J Physiol Renal Physiol. 2008 Sep;295(3):F818-25
references.pmid: 18632796
references.citation: Am J Physiol Renal Physiol. 2006 Feb;290(2):F542-9
references.pmid: 16189289
references.citation: Biochem Biophys Res Commun. 2000 Jan 19;267(2):577-80
references.pmid: 10631104
references.citation: Hypertension. 2004 Oct;44(4):424-8
references.pmid: 15314032
references.citation: Hypertension. 1999 Dec;34(6):1265-74
references.pmid: 10601129
references.citation: Am J Physiol Renal Physiol. 2004 Jul;287(1):F152-9
references.pmid: 15010356
references.citation: J Cardiovasc Pharmacol. 2006;47 Suppl 1:S37-42
references.pmid: 16785827
references.citation: Am J Physiol Renal Physiol. 2012 Dec 15;303(12):F1652-7
references.pmid: 23077099
references.citation: J Clin Invest. 2002 Jun;109(11):1417-27
references.pmid: 12045255
references.citation: J Biol Chem. 2000 Nov 24;275(47):36839-46
references.pmid: 10973964
references.citation: J Clin Invest. 2002 Jul;110(1):61-9
references.pmid: 12093889
references.citation: Curr Opin Crit Care. 2001 Dec;7(6):393-400
references.pmid: 11805541
references.citation: Hypertension. 2012 Feb;59(2):317-23
references.pmid: 22203739
references.citation: Am J Hypertens. 2011 Nov;24(11):1239-44
references.pmid: 21833043
references.citation: Am J Hypertens. 2012 Oct;25(10):1042-9
references.pmid: 22695507
references.citation: Hypertension. 2011 Apr;57(4):859-64
references.pmid: 21321306
references.citation: Am J Hypertens. 2011 Nov;24(11):1188
references.pmid: 22008968
references.citation: Am J Physiol. 1996 Jul;271(1 Pt 2):F143-9
references.pmid: 8760255
references.citation: Hypertension. 2011 Mar;57(3):355-62
references.pmid: 21282552
references.citation: Hypertension. 2004 Aug;44(2):223-9
references.pmid: 15226276
references.citation: Am J Physiol Renal Physiol. 2000 Jul;279(1):F12-23
references.pmid: 10894784
references.citation: Hypertension. 2008 Jun;51(6):1597-604
references.pmid: 18413493
references.citation: Arterioscler Thromb Vasc Biol. 2008 Jun;28(6):1151-7
references.pmid: 18388329
references.citation: Hypertension. 2002 Feb;39(2 Pt 2):316-22
references.pmid: 11882566
references.citation: Hypertension. 2009 Aug;54(2):261-9
references.pmid: 19546380
references.citation: J Clin Invest. 1986 Nov;78(5):1311-5
references.pmid: 3533999
references.citation: Curr Pharm Des. 2006;12(8):943-54
references.pmid: 16533161
references.citation: Hypertension. 1995 May;25(5):1111-5
references.pmid: 7737724