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The enzymes required for aldosterone synthesis from cholesterol are expressed in rat and human brains. The hypertension of
Dahl salt-sensitive (SS) rats is mitigated by the intracerebroventricular ( i.c.v .) infusion of antagonists of the mineralocorticoid receptor (MR) and downstream effectors of mineralocorticoid action, as
well as ablations of brain areas that also abrogate mineralocorticoidâsalt excess hypertension in normotensive rats. We used
real time RT-PCR to measure mRNA of aldosterone synthase and 11β-hydroxylase, the requisite enzymes for the last step in the
synthesis of aldosterone and corticosterone, respectively, MR and the determinants of MR ligand specificity, 11β-hydroxysteroid
dehydrogenase types 1 and 2 (11β-HSD1&2) and hexose-6-phosphate dehydrogenase (H6PDH). A combination of extraction and ELISA
was used to measure aldosterone concentrations in tissue and urine of SS and SpragueâDawley (SD) rats. Aldosterone synthase
mRNA expression was higher in the brains and lower in the adrenal glands of SS compared with SD rats. The amounts of mRNA
for MR, 11β-hydroxylase, 11β-HSD1&2 and H6PD were similar. Aldosterone concentrations were greater in brains of SS than SD
rats, yet, in keeping with the literature, the circulating and total aldosterone production of aldosterone in SS rats were
not. The selective inhibitor of aldosterone synthase, FAD286, was infused i.c.v . or subcutaneously in a cross-over blood pressure study in hypertensive SS rats further challenged by a high-salt diet. The
i.c.v . infusion of FAD286, at a dose that had no effect systemically, significantly and reversibly lowered blood pressure in SS
rats. Aldosterone synthesis in brains of SS rats is greater than in SD rats and is important in the genesis of their salt-sensitive
hypertension.