Disruption of the type 2 dopamine receptor gene causes a sodium-dependent increase in blood pressure in mice.
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.
Ueda
Atsushi
A
Department of Medicine and Molecular Science, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Ozono
Ryoji
R
Oshima
Tetsuya
T
Yano
Ai
A
Kambe
Masayuki
M
Teranishi
Yasuhiro
Y
Katsuki
Motoya
M
Chayama
Kazuaki
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics*; D001835:Body Weight; D018491:Dopamine Agonists / Q000494:pharmacology; D006973:Hypertension / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009318:Natriuresis / Q000187:drug effects / Q000235:genetics; D009638:Norepinephrine / Q000652:urine; D011188:Potassium / Q000378:metabolism; D019257:Quinpirole / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012982:Sodium, Dietary / Q000494:pharmacology* / Q000652:urine; D014556:Urine
D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D012982:Sodium, Dietary; D019257:Quinpirole; D011188:Potassium; D009638:Norepinephrine