title: [G protein kinase 4gammaA142V overexpression induced hypertension by downregulating D1 receptors in transgenic mice].
abstract: OBJECTIVE
  Abnormalities in dopamine production and receptor function have been described in human essential hypertension and rodent models of genetic hypertension. We investigated the role of G protein kinase (GRK) 4gamma in essential hypertension in GRK4gamma mutant A142V transgenic mice.
  
  
  METHODS
  Blood pressure, renal sodium excretion, D(1) receptor protein expression and phosphorylation were measured in GRK4gammaA142V transgenic mice and control mice. Moreover, the effects of GRK4 inhibition by antisense oligonucleotides on D(1) receptor expressions were determined in HK-2 cells.
  
  
  RESULTS
  As compared with their control mice, GRK4gammaA142V transgenic mice had higher blood pressure, lower D(1) receptor expression (0.6 +/- 0.2 vs. 1.5 +/- 0.2, P < 0.05), higher D(1) receptor phosphorylation [(65 +/- 7) DU vs. (35 +/- 7) DU, P < 0.05] in renal cortical membranes and the diuretic and natriuretic effects after stimulation of renal D(1) receptor were impaired in GRK4gammaA142V transgenic mice. Inhibition of GRK4 expression (0.60 +/- 0.10 vs. 1.30 +/- 0.09, P < 0.05) by GRK4 antisense oligonucleotides upregulated D(1) receptor expression (1.5 +/- 0.2 vs. 0.8 +/- 0.1, P < 0.05) in HK-2 cells.
  
  
  CONCLUSIONS
  Our results show that GRK4gammaA142V overexpression induced hypertension is mediated by dowregulated renal D(1) receptor expressions in GRK4gammaA142V transgenic mice.
authors.affiliation: Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing 400042, China. chunyuzeng01@163.com
authors.forename: Chun-yu
authors.initials: CY
authors.lastname: Zeng
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhi-wei
authors.initials: ZW
authors.lastname: Yang
authors.forename: Duo-fen
authors.initials: DF
authors.lastname: He
authors.forename: Cheng-ming
authors.initials: CM
authors.lastname: Yang
authors.forename: Laureano D
authors.initials: LD
authors.lastname: Asico
authors.forename: Robin A
authors.initials: RA
authors.lastname: Felder
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
mesh_terms: D000818:Animals; D001794:Blood Pressure; D015536:Down-Regulation; D005260:Female; D054771:G-Protein-Coupled Receptor Kinase 4 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016376:Oligonucleotides, Antisense; D010766:Phosphorylation; D017447:Receptors, Dopamine D1 / Q000378:metabolism
chemical_list: D016376:Oligonucleotides, Antisense; D017447:Receptors, Dopamine D1; D054771:G-Protein-Coupled Receptor Kinase 4; C517853:GRK4 protein, mouse