Collecting duct (pro)renin receptor targets ENaC to mediate angiotensin II-induced hypertension.
The (pro)renin receptor (PRR) is abundantly expressed in the collecting duct (CD) and the expression is further induced by angiotensin II (ANG II). The present study was conducted to investigate the role of CD PRR during ANG II-induced hypertension and to further explore the underlying mechanism. Radiotelemetry demonstrated that a 1-wk ANG II infusion gradually and significantly induced hypertensive response in floxed mice and this response was significantly attenuated in mice lacking PRR in the CD (termed CD PRR KO). ANG II infusion in floxed mice increased urinary renin activity and selectively induced renal medullary α-epithelial sodium channel (α-ENaC) mRNA and protein expression, all of which were blunted in the null mice. In cultured mpkCCD cells grown in Transwells, transepithelial Na+transport as measured by using a volt-ohmmeter was transiently stimulated by acute ANG II treatment, which was abolished by a PRR antagonist, PRO20. In a chronic setting, ANG II treatment induced α-ENaC mRNA expression in mpkCCD cells, which was similarly blocked by PRO20. Chronic intramedullary infusion of an ENaC inhibitor amiloride in rats significantly attenuated ANG II-induced hypertension. Overall, the present study suggests that CD PRR contributes to ANG II-induced hypertension at least partially via activation of renal medullary ENaC.
Institute of Hypertension, Sun Yat-Sen University School of Medicine, Guangzhou, China.|Department of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah.
Kexin
K
Peng
Institute of Hypertension, Sun Yat-Sen University School of Medicine, Guangzhou, China.|Department of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah.
Xiaohan
X
Lu
Institute of Hypertension, Sun Yat-Sen University School of Medicine, Guangzhou, China.|Department of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah.
Fei
F
Wang
Institute of Hypertension, Sun Yat-Sen University School of Medicine, Guangzhou, China.
Adam
A
Nau
Department of Internal Medicine, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China; and.
Ren
R
Chen
Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, Florida.
Shu-Feng
SF
Zhou
Institute of Hypertension, Sun Yat-Sen University School of Medicine, Guangzhou, China; Tianxin.Yang@hsc.utah.edu yangtxin@mail.sysu.edu.cn.|Department of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah.
Tianxin
T
Yang
D000804:Angiotensin II; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002478:Cells, Cultured; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012083:Renin / Q000494:pharmacology; D000093342:Prorenin Receptor
D053503:Epithelial Sodium Channels; C000595796:PRO20 peptide; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D000804:Angiotensin II; D012083:Renin; D000093342:Prorenin Receptor
(pro)renin receptor; angiotensin II; epithelial sodium channel; inner medullary collecting duct; renin activity