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: Xiaoyan Wang, Crisanto S Escano, Laureano Asico, John E Jones, Alan Barte, Yuen-Sum Lau, Pedro A Jose, Ines Armando
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 62 Issue 2 Pg. 295-301 (Aug 2013) ISSN: 1524-4563 [Electronic] United States
• PMID: 23753418 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Benzazepines
• Receptors, Dopamine D3
• SCH 23390
• Sodium Chloride, Dietary
• Receptors, Dopamine D5
• Sodium

Topics

• Animals
• Benzazepines (pharmacology)
• Hypertension (etiology, prevention & control)
• Immunohistochemistry
• Kidney (physiology)
• Mice
• Mice, Inbred C57BL
• Receptors, Dopamine D3 (analysis, physiology)
• Receptors, Dopamine D5 (analysis, physiology)
• Sodium (metabolism)
• Sodium Chloride, Dietary (administration & dosage)
• Up-Regulation