Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The practicability and tolerability of trilostane, a competitive inhibitor of 3 beta-hydroxysteroid-delta 5-dehydrogenase, for the therapy of primary aldosteronism was assessed in 1 patient with aldosterone-producing adenoma (APA) and 3 subjects with idiopathic adrenal hyperplasia (IHA). Trilostane afforded reduction of plasma levels of aldosterone, progesterone, deoxycorticosterone, 17-OH progesterone, cortisol, delta 4-androstenedione, and urinary excretion of 17-hydroxycorticosteroid. Conversely, circulating levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate, and urinary excretion of 17-ketosteroids were increased following this drug therapy. Suppression of mineralo- or glucocorticoid biosynthesis was accompanied by an increase in plasma renin activity. One patient with APA or 3 subjects with IHA showed slight or remarkable improvement of hypertension and hypokalemia. Based on these findings, efficacy and tolerability of trilostane appear to aid in the treatment of IHA.
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PMID:Primary aldosteronism treated by trilostane (3 beta-hydroxysteroid dehydrogenase inhibitor). 298 27

The brains of rats and humans express the enzymes required for the synthesis of aldosterone from cholesterol, including the 3beta-steroid dehydrogenase that catalyzes the conversion of pregnenolone to progesterone in the pathway of adrenal steroid synthesis. Salt-induced hypertension in the Dahl inbred salt-sensitive (SS/jr) rat is associated with normal to low levels of circulating aldosterone, yet it is abrogated by the central infusion of mineralocorticoid receptor antagonists. To test the hypothesis that de novo synthesis of aldosterone in the brain has a pathophysiological role in the salt-induced hypertension of the SS rat, the 3beta-steroid dehydrogenase antagonist trilostane was infused continuously intracerebroventricularly or subcutaneously in two different cohorts of Dahl SS/jr rats, one female, the other male, during and after the development of salt-induced hypertension. The doses of trilostane used had no effect on blood pressure when infused subcutaneously. Animals receiving vehicle intracerebroventricularly experienced a 30- to 45-mmHg increase in systolic blood pressure measured by tail cuff. The intracerebroventricular, but not subcutaneous, infusion of 0.3 microg/h trilostane effectively blocked the increase in systolic blood pressure and reversed the hypertension produced by drinking 0.9% saline. Trilostane was equally effective in female and male rats. Weight gain, serum aldosterone and corticosterone concentrations, and behavior assessed subjectively and by elevated plus maze were unchanged by the trilostane treatment. These studies suggest that the synthesis in the brain of a mineralocorticoid receptor agonist, probably aldosterone, is responsible in part for the salt-induced hypertension of the inbred Dahl SS/jr rat.
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PMID:Effect of 3beta-hydroxysteroid dehydrogenase inhibition by trilostane on blood pressure in the Dahl salt-sensitive rat. 1922 42