title: Activation of D4 dopamine receptor decreases angiotensin II type 1 receptor expression in rat renal proximal tubule cells.
abstract: The dopaminergic and renin-angiotensin systems interact to regulate blood pressure. Disruption of the D4 dopamine receptor gene in mice produces hypertension that is associated with increased renal angiotensin type 1 (AT1) receptor expression. We hypothesize that the D4 receptor can inhibit AT1 receptor expression and function in renal proximal tubule cells from Wistar-Kyoto (WKY) rats, but the D4 receptor regulation of AT1 receptor is aberrant in renal proximal tubule cells from spontaneously hypertensive rats (SHRs). The D4 receptor agonist, PD168077, decreased AT1 receptor protein expression in a time- and concentration-dependent manner in WKY cells. By contrast, in SHR cells, PD168077 increased AT1 receptor protein expression. The inhibitory effect of D4 receptor on AT1 receptor expression in WKY cells was blocked by a calcium channel blocker, nicardipine, or calcium-free medium, indicating that calcium is involved in the D4 receptor-mediated signaling pathway. Angiotensin II increased Na(+)-K(+) ATPase activity in WKY cells. Pretreatment with PD168077 decreased the stimulatory effect of angiotensin II on Na(+)-K(+) ATPase activity in WKY cells. In SHR cells, the inhibitory effect of D4 receptor on angiotensin II-mediated stimulation of Na(+)-K(+) ATPase activity was aberrant; pretreatment with PD168077 augmented the stimulatory effect of AT1 receptor on Na(+)-K(+) ATPase activity in SHR cells. This was confirmed in vivo; pretreatment with PD128077 for 1 week augmented the antihypertensive and natriuretic effect of losartan in SHRs but not in WKY rats. We suggest that an aberrant interaction between D4 and AT1 receptors may play a role in the abnormal regulation of sodium excretion in hypertension.
authors.affiliation: From the Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); Chongqing Institute of Cardiology, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); and Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (X.W., L.D.A., P.A.J.).
authors.forename: Ken
authors.initials: K
authors.lastname: Chen
authors.affiliation: From the Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); Chongqing Institute of Cardiology, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); and Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (X.W., L.D.A., P.A.J.).
authors.forename: Kun
authors.initials: K
authors.lastname: Deng
authors.affiliation: From the Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); Chongqing Institute of Cardiology, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); and Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (X.W., L.D.A., P.A.J.).
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: From the Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); Chongqing Institute of Cardiology, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); and Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (X.W., L.D.A., P.A.J.).
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: From the Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); Chongqing Institute of Cardiology, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); and Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (X.W., L.D.A., P.A.J.).
authors.forename: Shuo
authors.initials: S
authors.lastname: Zheng
authors.affiliation: From the Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); Chongqing Institute of Cardiology, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); and Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (X.W., L.D.A., P.A.J.).
authors.forename: Hongmei
authors.initials: H
authors.lastname: Ren
authors.affiliation: From the Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); Chongqing Institute of Cardiology, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); and Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (X.W., L.D.A., P.A.J.).
authors.forename: Duofen
authors.initials: D
authors.lastname: He
authors.affiliation: From the Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); Chongqing Institute of Cardiology, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); and Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (X.W., L.D.A., P.A.J.).
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.affiliation: From the Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); Chongqing Institute of Cardiology, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); and Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (X.W., L.D.A., P.A.J.).
authors.forename: Laureano D
authors.initials: LD
authors.lastname: Asico
authors.affiliation: From the Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); Chongqing Institute of Cardiology, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); and Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (X.W., L.D.A., P.A.J.).
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
authors.affiliation: From the Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); Chongqing Institute of Cardiology, Chongqing, People's Republic of China (K.C., K.D., Z.W., S.Z., H.R., D.H., Y.H., C.Z.); and Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (X.W., L.D.A., P.A.J.). cyzeng1@hotmail.com.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D015151:Immunoblotting; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D018613:Microscopy, Confocal; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis*; D050638:Receptors, Dopamine D4 / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology
chemical_list: D044140:Receptor, Angiotensin, Type 1; D050638:Receptors, Dopamine D4
keywords: angiotensin type 1 receptor; dopamine D4 receptor; hypertension