Role of mineralocorticoid action in the brain in salt-sensitive hypertension

Summary 1. The mechanisms by which excessive salt causes hypertension involve more than retention of sodium and water by the kidneys and are far from clear. Mineralocorticoids act centrally to increase salt appetite, sympathetic drive and vasopressin release, resulting in hypertension that is prevented by the central infusion of mineralocorticoid receptor (MR) antagonists. The MR has similar affinity for aldosterone and the glucocorticoids corticosterone or cortisol. Specificity is conferred in transport epithelia by the colocalization of the MR with 11β‐hydroxysteroid dehydrogenase Type 2. Coexpression also occurs in some neurons, notably those of the nucleus tractus solitarius that are activated by sodium depletion and aldosterone and mediate salt‐seeking behaviour. 2. The salt‐induced hypertension of the Dahl salt‐sensitive rat is mitigated by the central infusion of a mineralocorticoid antagonist even though circulating aldosterone is normal or reduced in salt‐sensitive (SS). Contrary to reports that salt appetite in the Dahl salt‐sensitive rat is depressed, we found that it is increased compared with that in Spraque‐Dawley rats. 3. Extra‐adrenal aldosterone synthesis in the brain occurs in minute amounts that could only be relevant locally. Expression of aldosterone synthase mRNA and aldosterone concentrations in the brain of Dahl salt‐sensitive rats are increased compared with Spraque‐Dawley rats. The central infusion of inhibitors of aldosterone synthesis lowers salt‐induced hypertension in the Dahl salt‐sensitive rat, suggesting a role for excessive Dahl salt‐sensitive synthesis in the brain. Brain MR, particularly those in the paraventricular nuclei, regulate inflammatory processes that are exacerbated by sodium and lead to cardiovascular dysfunction.