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Regulation of Aldosterone Synthase Gene Expression in the Rat Adrenal Gland and Central Nervous System by Sodium and Angiotensin II

Medical Research Council Blood Pressure Group (P.Y., S.M.M., R.F., J.M.C.C., E.D.), Division of Cardiovascular and Medical Sciences, Western Infirmary, Glasgow, Scotland G11 6NT, United Kingdom; and Molecular Endocrinology, Molecular Medicine Centre (C.J.K., J.R.S.), Western General Hospital, Edinburgh, Scotland EH4 2XU, United Kingdom

Address all correspondence and requests for reprints to: Dr. Eleanor Davies, Medical Research Council Blood Pressure Group, Division of Cardiovascular and Medical Sciences, Western Infirmary, Glasgow, Scotland G11 6NT, United Kingdom. E-mail: ed18g{at}clinmed.gla.ac.uk.

We have developed a highly sensitive QRT-PCR method for the measurement of CYP11B1 (11ß-hydroxylase) and CYP11B2 (aldosterone synthase) mRNAs to study their expression in the rat brain in response to dietary sodium manipulation and angiotensin (Ang)II infusion. Male Wistar Kyoto rats (n = 6) were fed normal, high, or low sodium diets for 12 d or were administered AngII or vehicle for 7 d. CYP11B2 and CYP11B1 expression was measured in RNA from adrenal gland and discrete brain regions using real-time QRT-PCR. Sodium restriction increased adrenal CYP11B2 expression 57-fold from 1.0 x 10⁵ ± 0.6 x 10⁵ to 57 x 10⁵ ± 22 x 10⁵ copies/µg RNA (mean ± SEM; P < 0.05);in the hippocampus, 14-fold from 5.4 x 10² ± 0.8 x 10² to 74 x 10² ± 31 x 10² copies/µg RNA (P < 0.05); and in the cerebellum, 5-fold from 1.9 x 10³ ± 0.7 x 10³ to 9.9 x 10³ ± 3.0 x 10³ copies/µg RNA (P < 0.01). CYP11B2 gene expression in the brainstem and hypothalamus was not affected. High-sodium diet reduced adrenal CYP11B2 expression to 0.19 x 10⁵ ± 0.1 x 10⁵ copies/µg RNA (P < 0.05) but did not affect central nervous system (CNS) expression significantly. AngII significantly increased adrenal CYP11B2 expression but did not affect CNS expression. Brain CYP11B1 mRNA levels were 10- to 1000-fold higher than CYP11B2 but were unaffected by dietary sodium or AngII. To summarize, we have identified a local CYP11B2 response to sodium depletion in the hippocampus and cerebellum. This is the first such regulation of CYP11B2 transcription to be identified in the CNS.

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