title: Regulation of blood pressure, oxidative stress and AT1R by high salt diet in mutant human dopamine D5 receptor transgenic mice.
abstract: Humans have dopamine D5 receptors (hD5R) with single-nucleotide polymorphisms and a diminished function. We generated hD5(F173L) cDNA that has a decreased response to D5R agonist-mediated increase in cAMP production and increased production of reactive oxygen species, relative to wild-type hD5R (hD5(WT)) cDNA expressed in Chinese hamster ovary cells. To investigate the role of hD5(F173L) in the pathogenesis of salt-sensitive hypertension, we generated transgenic mice overexpressing hD5(F173L) or hD5(WT) and fed them normal (0.8% NaCl) or high (4% NaCl) salt diet. On normal salt diet, the blood pressure, and renal NADPH oxidase activity and angiotensin type 1 receptor (AT1R) expression were higher in hD5(F173L) than hD5(WT) transgenic mice. After 2 weeks on high salt diet, the blood pressure and renal NADPH oxidase activity, but not AT1R expression, were increased in hD5(F173L) but not in hD5(WT) transgenic mice. Candesartan, an AT1R antagonist, decreased the blood pressure and NADPH oxidase activity in hD5(F173L) but not in hD5(WT) transgenic mice. We suggest that the ability of the hD5R to negatively regulate the renal NADPH oxidase activity and AT1R function may have important implications in the pathogenesis of salt-sensitive blood pressure. However, the mechanisms involved in regulating the balance of renal D5R and AT1R function in the oxidative stress-mediated salt-sensitive blood pressure remain to be determined.
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing, People's Republic China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing, People's Republic China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Wang
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing, People's Republic China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing, People's Republic China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing, People's Republic China.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing, People's Republic China.
authors.forename: Zihao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Jones
authors.affiliation: 1] Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA [2] Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing, People's Republic China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D016466:CHO Cells; D003412:Cricetulus; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009249:NADP / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D050641:Receptors, Dopamine D5 / Q000235:genetics / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D017673:Sodium Chloride, Dietary; D050641:Receptors, Dopamine D5; D009249:NADP