title: Upregulation of renal D5 dopamine receptor ameliorates the hypertension in D3 dopamine receptor-deficient mice.
abstract: D3 dopamine receptor (D3R)-deficient mice have renin-dependent hypertension associated with sodium retention, but the hypertension is mild. To determine whether any compensatory mechanisms in the kidney are involved in the regulation of blood pressure with disruption of Drd3, we measured the renal protein expression of all dopamine receptor subtypes (D1R, D2R, D4R, and D5R) in D3R homozygous (D3(-/-)) and heterozygous (D3(+/-)) knockout mice and their wild-type (D3(+/+)) littermates. The renal immunohistochemistry and protein expression of D5R were increased (n=5/group) in D3(-/-) mice; renal D4R protein expression was decreased, whereas renal protein expressions of D1R and D2R were similar in both groups. Renal D5R protein expression was also increased in D3(+/-) (n=5/group) relative to D3(+/+) mice, whereas D1R, D2R, and D4R protein expressions were similar in D3(+/-) and D3(+/+) mice. The increase in renal D5R protein expression was abolished when D3(-/-) mice were fed a high-salt diet. Treatment with the D1-like receptor antagonist, SCH23390, increased the blood pressure in anesthetized D3(-/-) but not D3(+/+) mice (n=4/group), suggesting that the renal upregulation of D5R may have minimized the hypertension in D3(-/-) mice. The renal D5R protein upregulation was not caused by increased transcription because renal mRNA expression of D5R was similar in D3(-/-) and D3(+/+) mice. Our findings suggest that the renal upregulation of D5R may have minimized the hypertension that developed in D3(-/-) mice.
authors.affiliation: Department of Medicine, University of Maryland, School of Medicine, 20 Penn St, Baltimore, MD 21201, USA. xwang1@medicine.umaryland.edu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Crisanto S
authors.initials: CS
authors.lastname: Escano
authors.forename: Laureano
authors.initials: L
authors.lastname: Asico
authors.forename: John E
authors.initials: JE
authors.lastname: Jones
authors.forename: Alan
authors.initials: A
authors.lastname: Barte
authors.forename: Yuen-Sum
authors.initials: YS
authors.lastname: Lau
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
authors.forename: Ines
authors.initials: I
authors.lastname: Armando
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D006973:Hypertension / Q000209:etiology* / Q000517:prevention & control; D007150:Immunohistochemistry; D007668:Kidney / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D050637:Receptors, Dopamine D3 / Q000032:analysis / Q000502:physiology*; D050641:Receptors, Dopamine D5 / Q000032:analysis / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D015854:Up-Regulation
chemical_list: D001552:Benzazepines; D050637:Receptors, Dopamine D3; C534628:SCH 23390; D017673:Sodium Chloride, Dietary; D050641:Receptors, Dopamine D5; D012964:Sodium
keywords: blood pressure; dopamine; mice, knockout; receptors, dopamine