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Inappropriate activation of the renin-angiotensin system, which plays a central role in the regulation of blood pressure, electrolyte, and volume homeostasis, may represent a major risk factor for hypertension, heart attack, and stroke.Mounting evidence from clinical studies has demonstrated an inverse relationship between circulating vitamin D levels and the blood pressure and/or plasma renin activity, but the mechanism is not understood.We show here that renin expression and plasma angiotensin II production were increased severalfold in vitamin D receptor-null (VDR-null) mice, leading to hypertension, cardiac hypertrophy, and increased water intake.However, the salt-and volume-sensing mechanisms that control renin synthesis are still intact in the mutant mice.In wild-type mice, inhibition of 1,25-dihydroxyvitamin D 3 1,25(OH) 2 D 3 synthesis also led to an increase in renin expression, whereas 1,25(OH) 2 D 3 injection led to renin suppression.We found that vitamin D regulation of renin expression was independent of calcium metabolism and that 1,25(OH) 2 D 3 markedly suppressed renin transcription by a VDR-mediated mechanism in cell cultures.Hence, 1,25(OH) 2 D 3 is a novel negative endocrine regulator of the renin-angiotensin system.Its apparent critical role in electrolytes, volume, and blood pressure homeostasis suggests that vitamin D analogues could help prevent or ameliorate hypertension.
Li et al. (Mon,) studied this question.