Evidence for glucocorticoid-mediated hypertension after uninephrectomy.

Recently, evidence was presented that uninephrectomy induces salt-sensitive hypertension in rats. The increase in blood pressure was abrogated by a mineralocorticoid receptor antagonist but not by an aldosterone synthase inhibitor. Here, we hypothesize that mineralocorticoid receptor activation occurred by an 11beta-hydroxy-glucocorticosteroid, as a consequence of dysregulated 11beta-hydroxysteroid dehydrogenase enzymes.

High salt intake down-regulates colonic mineralocorticoid receptors, epithelial sodium channels and 11β-hydroxysteroid dehydrogenase type 2.

Besides the kidneys, the gastrointestinal tract is the principal organ responsible for sodium homeostasis. For sodium transport across the cell membranes the epithelial sodium channel (ENaC) is of pivotal relevance. The ENaC is mainly regulated by mineralocorticoid receptor mediated actions.