title: Prostaglandin E-prostanoid4 receptor mediates angiotensin II-induced (pro)renin receptor expression in the rat renal medulla.
abstract: Angiotensin II (Ang II) stimulates (pro)renin receptor (PRR) expression in the renal collecting duct, triggering the local renin response in the distal nephron. Our recent study provided evidence for involvement of cyclooxygenase-2-prostaglandin E2 pathway in Ang II-dependent stimulation of PRR expression in the collecting duct. Here, we tested the role of E-prostanoid (EP) subtypes acting downstream of cyclooxygenase-2 in this phenomenon. In primary rat inner medullary collecting duct cells, Ang II treatment for 12 hours induced a 1.8-fold increase in the full-length PRR protein expression. To assess the contribution of EP receptor, the cell was pretreated with specific EP receptor antagonists: SC-51382 (for EP1), L-798106 (for EP3), L-161982 (for EP4), and ONO-AE3-208 (ONO, a structurally distinct EP4 antagonist). The upregulation of PRR expression by Ang II was consistently abolished by L-161982 and ONO and partially suppressed by SC-51382 but was unaffected by L-798106. The PRR expression was also significantly elevated by the EP4 agonist CAY10598 in the absence of Ang II. Sprague-Dawley rats were subsequently infused for 1 or 2 weeks with vehicle, Ang II alone, or in combination with ONO. Ang II infusion induced parallel increases in renal medullary PRR protein and renal medullary and urinary renin activity and total renin content, all of which were blunted by ONO. Both tail cuff plethysmography and telemetry demonstrated attenuation of Ang II hypertension by ONO. Overall, these results have established a crucial role of the EP4 receptor in mediating the upregulation of renal medullary PRR expression and renin activity during Ang II hypertension.
authors.affiliation: From the Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China (F.W., X.L., K.P., T.Y.); Department of Internal Medicine, University of Utah, Salt Lake City (F.W., X.L., T.Y.); Veterans Affairs Medical Center, Salt Lake City, UT (F.W., X.L., T.Y.); Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China (Y.D.); Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa (S.-F.Z.); and Department of Nephrology, Nanjing Children's Hospital, Affiliated to Nanjing Medical University, Nanjing, China (A.Z.).
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: From the Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China (F.W., X.L., K.P., T.Y.); Department of Internal Medicine, University of Utah, Salt Lake City (F.W., X.L., T.Y.); Veterans Affairs Medical Center, Salt Lake City, UT (F.W., X.L., T.Y.); Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China (Y.D.); Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa (S.-F.Z.); and Department of Nephrology, Nanjing Children's Hospital, Affiliated to Nanjing Medical University, Nanjing, China (A.Z.).
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Lu
authors.affiliation: From the Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China (F.W., X.L., K.P., T.Y.); Department of Internal Medicine, University of Utah, Salt Lake City (F.W., X.L., T.Y.); Veterans Affairs Medical Center, Salt Lake City, UT (F.W., X.L., T.Y.); Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China (Y.D.); Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa (S.-F.Z.); and Department of Nephrology, Nanjing Children's Hospital, Affiliated to Nanjing Medical University, Nanjing, China (A.Z.).
authors.forename: Kexin
authors.initials: K
authors.lastname: Peng
authors.affiliation: From the Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China (F.W., X.L., K.P., T.Y.); Department of Internal Medicine, University of Utah, Salt Lake City (F.W., X.L., T.Y.); Veterans Affairs Medical Center, Salt Lake City, UT (F.W., X.L., T.Y.); Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China (Y.D.); Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa (S.-F.Z.); and Department of Nephrology, Nanjing Children's Hospital, Affiliated to Nanjing Medical University, Nanjing, China (A.Z.).
authors.forename: Yaomin
authors.initials: Y
authors.lastname: Du
authors.affiliation: From the Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China (F.W., X.L., K.P., T.Y.); Department of Internal Medicine, University of Utah, Salt Lake City (F.W., X.L., T.Y.); Veterans Affairs Medical Center, Salt Lake City, UT (F.W., X.L., T.Y.); Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China (Y.D.); Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa (S.-F.Z.); and Department of Nephrology, Nanjing Children's Hospital, Affiliated to Nanjing Medical University, Nanjing, China (A.Z.).
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Zhou
authors.affiliation: From the Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China (F.W., X.L., K.P., T.Y.); Department of Internal Medicine, University of Utah, Salt Lake City (F.W., X.L., T.Y.); Veterans Affairs Medical Center, Salt Lake City, UT (F.W., X.L., T.Y.); Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China (Y.D.); Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa (S.-F.Z.); and Department of Nephrology, Nanjing Children's Hospital, Affiliated to Nanjing Medical University, Nanjing, China (A.Z.).
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhang
authors.affiliation: From the Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China (F.W., X.L., K.P., T.Y.); Department of Internal Medicine, University of Utah, Salt Lake City (F.W., X.L., T.Y.); Veterans Affairs Medical Center, Salt Lake City, UT (F.W., X.L., T.Y.); Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China (Y.D.); Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa (S.-F.Z.); and Department of Nephrology, Nanjing Children's Hospital, Affiliated to Nanjing Medical University, Nanjing, China (A.Z.). Tianxin.Yang@hsc.utah.edu.
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D000093342:Prorenin Receptor
chemical_list: D011956:Receptors, Cell Surface; D011982:Receptors, Prostaglandin; D058309:Receptors, Prostaglandin E, EP4 Subtype; D000804:Angiotensin II; D000093342:Prorenin Receptor
keywords: dinoprostone