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.