Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Outline of Final Research Achievements |
To reveal the mechanism of nocturnal hypertension, we generated kidney-specific Hsd11b2 knockout mice. The knockout mice exhibited nocturnal hypertension, and we detected an increase in renal membrane expressions of cleaved ENaCα and T53-phosphorylated NCC in the knockout mice. Chronic administration of amiloride and high-KCl diet significantly decreased mean blood pressure in the knockout mice, which was accompanied with the correction of hypokalemia and the resultant decrease in NCC phosphorylation. Accordingly, a NCC blocker hydrochlorothiazide significantly decreased mean blood pressure in the knockout mice. Chronic administration of MR antagonist spironolactone significantly decreased mean blood pressure of the knockout mice along with downregulation of cleaved ENaCα and phosphorylated NCC expression in the knockout kidney. Our data suggest that kidney-specific deficiency of HSD11B2 leads to nocturnal hypertension, which is attributed to MR-ENaC-NCC activation in the kidney.
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