High blood pressure but normal oxidative stress in D3 dopamine receptor deficient mice

Abstract

To determine if renal oxidative stress is involved in the regulation of blood pressure (BP) upon disruption of D3R, we measured the BP (telemetry) and indices of oxidative stress in D3R−/−, D3+/− and their wild type (D3+/+) mice on normal (0.8% NaCl) or high (4% NaCl) salt diet for one week. Systolic BP (SBP) was higher in D3‐/‐ and D3+/− relative to D3+/+ mice on normal salt diet. NOX1 (101±10 % of D3+/+ mice), NOX2 (101±8) and NOX4 (120±16) was similar in D3−/− and D3+/+ mice. CuZnSOD expression was increased (135±9, P<0.05, n=5), while the EcSOD and MnSOD were unchanged in D3−/− relative to D3+/+ mice. Nitrotyrosine (NT) was not altered in D3−/− (107±30). Urinary isoprostane excretion tended to be lower in D3−/− (445±106 pg/mg of creatinine) than D3+/+ (852±213), but the difference did not reach statistical significance. In D3+/− mice, NOX1 and NOX4 were unchanged but NOX2 (70±8, n=6) was slightly decreased. NT was similar in D3+/− and D3 +/+ mice. On high salt diet, SBP was increased more than 10% over baseline in D3−/− mice but not in D3+/+ mice. NOX1, NOX2, and NOX4 were not altered while NT was decreased (49±8, P<0.05, n=4) and EcSOD was increased (145±1) in D3−/− relative to D3+/+ mice. Thus, the hypertension and salt sensitivity observed in D3−/− and D3+/− mice are not associated with increased renal oxidative stress and compensatory mechanisms may be involved in maintaining normal production of ROS.