Background: Dopamine 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. Methods: The function of D2Rs was investigated in mice disrupted with D2R gene (D2KO mice). Six-week-old male D 2KO 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 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 D 2KO 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. Conclusions: These 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. © 2003 American Journal of Hypertension, Ltd.
Ueda, A., Ozono, R., Oshima, T., Yano, A., Kambe, M., Teranishi, Y., … Chayama, K. (2003). Disruption of the type 2 dopamine receptor gene causes a sodium-dependent increase in blood pressure in mice. American Journal of Hypertension, 16(10), 853–858. https://doi.org/10.1016/S0895-7061(03)01013-6