2003年10月
Disruption of the type 2 dopamine receptor gene causes a sodium-dependent increase in blood pressure in mice
AMERICAN JOURNAL OF HYPERTENSION
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- 巻
- 16
- 号
- 10
- 開始ページ
- 853
- 終了ページ
- 858
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1016/S0895-7061(01)01013-6
- 出版者・発行元
- ELSEVIER SCIENCE INC
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 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.
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 D2KO 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. (C) 2003 American Journal of Hypertension, Ltd.
Methods: The 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.
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 D2KO 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. (C) 2003 American Journal of Hypertension, Ltd.
- リンク情報
- ID情報
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- DOI : 10.1016/S0895-7061(01)01013-6
- ISSN : 0895-7061
- Web of Science ID : WOS:000185749000010