Effect of 3β-hydroxysteroid dehydrogenase inhibition by trilostane on blood pressure in the Dahl salt-sensitive rat

Elise P. Gomez-Sanchez, Jacqueline Samuel, Gaston Vergara, Naveed Ahmad

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

The brains of rats and humans express the enzymes required for the synthesis of aldosterone from cholesterol, including the 3β-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 3β-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 μg/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.

Original languageEnglish (US)
Pages (from-to)R389-R393
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume288
Issue number2 57-2
DOIs
StatePublished - Feb 2005

Keywords

  • 11β-hydroxylase
  • Aldosterone synthesis
  • Brain
  • Corticosterone
  • Hypertension

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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