Regulation of aldosterone synthase gene expression in the rat adrenal gland and central nervous system by sodium and angiotensin II

Abstract

We have developed a highly sensitive QRT-PCR method for the measurement of CYP11B1 (11β-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 × 105 ± 0.6 × 105 to 57 × 105 ± 22 × 105 copies/μgRNA (mean ± SEM; P < 0.05);in the hippocampus, 14-fold from 5.4 × 102 ± 0.8 × 102 to 74 × 102 ± 31 × 102 copies/μg RNA (P < 0.05); and in the cerebellum, 5-fold from 1.9 × 103 ± 0.7 × 103 to 9.9 × 103 ± 3.0 × 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 × 105 ± 0.1 × 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.