Glucocorticoids and blood pressure: a role for the cortisol/cortisone shuttle in the control of vascular tone in man

Clin Sci (Lond). 1992 Aug;83(2):171-8. doi: 10.1042/cs0830171.

Abstract

1. 11 beta-Hydroxysteroid dehydrogenase converts cortisol to inactive cortisone in man. In distal renal tubules, this inactivation protects mineralocorticoid receptors from cortisol. Congenital 11 beta-hydroxysteroid dehydrogenase deficiency and inhibition of 11 beta-hydroxysteroid dehydrogenase by liquorice or carbenoxolone result in cortisol-dependent hypokalaemia and hypertension. 2. 11 beta-Hydroxysteroid dehydrogenase is expressed in vascular smooth muscle. Both glucocorticoids and mineralocorticoids potentiate vascular responses to noradrenaline. 11 beta-Hydroxysteroid dehydrogenase activity may therefore influence vascular tone. 3. Experiments were performed in healthy subjects with and without 7 days of oral administration of 11 beta-hydroxysteroid dehydrogenase inhibitors (liquorice or carbenoxolone), and in a patient with congenital 11 beta-hydroxysteroid dehydrogenase deficiency. We measured the following parameters: dermal vasoconstriction after topical application of cortisol, forearm blood flow during brachial artery infusion of cortisol or noradrenaline, and blood pressure during systemic infusion of noradrenaline. 4. Cortisol-induced dermal vasoconstriction was increased by liquorice (23 +/- 6 to 52 +/- 7 units; P < 0.04) and in congenital 11 beta-hydroxysteroid dehydrogenase deficiency (87 units). In congenital 11 beta-hydroxysteroid dehydrogenase deficiency intraarterial infusion of cortisol caused vasoconstriction (20% reduction in blood flow in the infused arm) and accentuated the response to application of lower-body negative pressure, which stimulates sympathetically mediated vasoconstriction (35% reduction). However, intra-arterial infusion of cortisol had no effect in healthy subjects either with or without administration of liquorice. 5. Carbenoxolone potentiated both noradrenaline induced forearm vasoconstriction (P < 0.01) and pressor response (P < 0.001). 6. We conclude that 11 beta-hydroxysteroid dehydrogenase modulates the access of cortisol to vascular receptors and thereby influences vascular sensitivity to noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Case Reports
  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenases
  • Adult
  • Blood Pressure / physiology*
  • Carbenoxolone / pharmacology
  • Cortisone / physiology
  • Double-Blind Method
  • Female
  • Glucocorticoids / physiology*
  • Glycyrrhiza
  • Humans
  • Hydrocortisone / metabolism
  • Hydrocortisone / pharmacology
  • Hydrocortisone / physiology
  • Hydroxysteroid Dehydrogenases / antagonists & inhibitors
  • Hydroxysteroid Dehydrogenases / deficiency
  • Kidney / drug effects
  • Male
  • Muscle, Smooth, Vascular / drug effects
  • Norepinephrine / metabolism
  • Norepinephrine / pharmacology
  • Plants, Medicinal
  • Skin / blood supply
  • Vasoconstriction / drug effects

Substances

  • Glucocorticoids
  • Hydroxysteroid Dehydrogenases
  • 11-beta-Hydroxysteroid Dehydrogenases
  • Carbenoxolone
  • Cortisone
  • Hydrocortisone
  • Norepinephrine