Disruption of the type 2 dopamine receptor gene causes a sodium-dependent increase in blood pressure in mice

Abstract

BackgroundDopamine D2 receptors (D2Rs) are expressed in the kidney. It has not been determined whether D2Rs are involved in the mechanism of sodium handling and blood pressure (BP) control. MethodsThe function of D2Rs was investigated in mice disrupted with D2R gene (D2KO mice). Six-week-old male D2KO mice and wild-type (WT) mice were fed high-salt (4% NaCl) or low-salt (0.01% NaCl) diets for 8 weeks. ResultsBefore starting the metabolic diet, there were no significant differences in body weight, food consumption, and 24-h urine excretions of creatinine, sodium and potassium. The high-salt diet caused a significant elevation in systolic BP in D2KO mice but not in WT mice. Calculation of sodium and potassium balances revealed a significantly high level of sodium retention in D2KO mice placed on the high-salt diet. Twenty-four-hour urine norepinephrine excretions and heart rates, indicators of sympathetic activity, were not different in D2KO and WT mice on the high-salt diet. Administration of nemonapride, a specific D2-like receptor antagonist, to WT mice given 0.9% NaCl in drinking water caused suppression of urinary sodium excretion but had no effect in mice without salt loading. ConclusionsThese results suggest that D2 receptors promote sodium excretion during a period of high salt intake. A defect in this mechanism may result in sodium-dependent BP elevation.