Synthesis of aldosterone in the brain contributes to the hypertension in the Dahl salt sensitive rat

Despite low or normal plasma aldo levels, the salt‐induced hypertension in Dahl SS rats is mitigated by the same pharmacological maneuvers and brain ablations that prevent mineralocorticoid‐salt excess hypertension. We found that all enzymes required for de novo synthesis of aldo are expressed in rat and human brain and that aldo is synthesized in the normal rat brain in vivo and in vitro in quantities that suggest autocrine or paracrine functions. mRNA for aldo synthase was measured by real time RT‐PCR and aldo by an extraction/ELISA assay in brains. SS rat brains had significantly greater amounts of aldo synthase mRNA in the brain stem, hypothalamus, hippocampus and cerebellum and aldo concentrations compared to control brains, though SS plasma aldo levels tended to be lower. The central infusion of the specific aldo synthase enzyme inhibitor, FAD286, significantly and reversibly lowered the blood pressure of SS rats. Many hypertensive patients benefit from MR antagonists, even though plasma levels of aldo are normal to low. As MR are most abundant in the hippocampus, where they mediate trophic responses necessary for learning and memory, it is important to determine the relevance of this model to human hypertension and devise more specific methods of blood pressure control. This work was supported by Medical Research funds from the Department of Veterans Affairs and NIH grants HL27255 and HL75321.