Abstract 370: Upregulation of Renal D5 Dopamine Receptor Ameliorates Hypertension in D3 Deficient Mice
D3 dopamine receptor (D3R) deficient mice have renin-dependent hypertension but the hypertension is mild and is not associated with oxidative stress. In order to determine if any compensatory mechanism in the kidney is involved in the regulation of blood pressure with disruption of D3R, we measured the renal protein expression of dopamine receptors in D3R homozygous (D3-/-) and heterozygous (D3+/-) knockout mice and their wild type (D3+/+) littermates. D5 dopamine receptor (D5R) (169±23%, reported as % of D3+/+, n=5/group) expression was increased but D4 dopamine receptors protein expression (59±8%) was decreased, while no significant changes were found with D1 and D2 dopamine receptors. Immunocytochemistry showed a stronger renal staining of D5R but without a change in renal tubule cell distribution in D3-/- relative to D3+/+ mice. D5R abundance was also increased in D3+/- (205±30%, n=5/group) relative to D3+/+ mice, while D1R abundance was similar between D3+/- and D3+/+ mice. The increase in D5R expression was abolished while blood pressure was increased further in D3-/- mice fed a high salt diet. Treatment of the D1-like (including D1 and D5 receptors) antagonist, SCH23390, increased the blood pressure to a greater extent in anesthetized D3-/- mice than in D3+/+ mice (n=4/group), suggesting that the upregulation of D5R may modulate the hypertension in mice caused by the disruption of D3R. Since dopamine inhibits the NADPH oxidase-induced production of reactive oxygen species (ROS) via the D5R, we also measured the protein expression of NOXs in the kidney and isoprostane in the urine. No NADPH oxidase subunit was increased in D3-/- and D3+/- mice relative to D3+/+ mice fed a normal or salt high salt diet, and urinary isoprostane excretion was also similar in D3-/- and D3+/+ mice. Our findings suggest that the upregulation of D5R may minimize the hypertension and prevent oxidative stress in D3-/- mice.
- © 2012 by American Heart Association, Inc.