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

Abstract Background Dopamine D 2 receptors (D 2 Rs) are expressed in the kidney. It has not been determined whether D 2 Rs are involved in the mechanism of sodium handling and blood pressure (BP) control. Methods The function of D 2 Rs was investigated in mice disrupted with D 2 R gene (D 2 KO mice). Six-week-old male D 2 KO mice and wild-type (WT) mice were fed high-salt (4% NaCl) or low-salt (0.01% NaCl) diets for 8 weeks. Results Before 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 D 2 KO mice but not in WT mice. Calculation of sodium and potassium balances revealed a significantly high level of sodium retention in D 2 KO mice placed on the high-salt diet. Twenty-four-hour urine norepinephrine excretions and heart rates, indicators of sympathetic activity, were not different in D 2 KO and WT mice on the high-salt diet. Administration of nemonapride, a specific D 2 -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. Conclusions These results suggest that D 2 receptors promote sodium excretion during a period of high salt intake. A defect in this mechanism may result in sodium-dependent BP elevation.