Glucocorticoids and vascular reactivity

Curr Vasc Pharmacol. 2004 Jan;2(1):1-12. doi: 10.2174/1570161043476483.

Abstract

Corticosteroid hormones play an important role in the control of vascular smooth muscle tone by their permissive effects in potentiating vasoactive responses to catecholamines through glucocorticoid receptors. Increased cortisol response has been associated with an increase in arterial contractile sensitivity to norepinephrine and vascular resistance. Glucocorticoids regulate vascular reactivity by acting on both endothelial and vascular smooth muscle cells. Both glucocorticoid receptor protein and mRNA have been identified in endothelial and vascular smooth muscle cells. In endothelial cells. glucocorticoids suppress the production of vasodilators. such as prostacyclin and nitric oxide. In vascular smooth muscle cells. glucocorticoids enhance agonist-mediated pharmacomechanical coupling at multiple levels. The effect of glucocorticoids on vascular reactivity is regulated by 11 beta-hydroxysteroid dehydrogenase (11beta-SD). The presence of 11beta-HSD in many tissues suggests that it modulates the access of corticosteroids to their receptors at both renal and extra-renal sites. The two 11beta-HSD isozymes catalyze the interconversion of cortisol and cortisone. Type 11beta-HSD has bidirectional activity, while the type 2 mainly converts cortisol into cortisone, the biologically inactive form. Both type 1 and type 2 11beta-HSD have been found in vascular endothelial and smooth muscle cells, suggesting that abnormal 11B-HSD expression may play a pathogenic role in the common forms of hypertension. In this article, we review possible mechanisms involved in the glucocorticoid-mediated potentiation of vascular reactivity, its regulation by 11beta-HSD, and their physiological and pathophysiological significance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenases / metabolism
  • 11-beta-Hydroxysteroid Dehydrogenases / physiology*
  • Animals
  • Blood Pressure / drug effects
  • Endothelium, Vascular* / drug effects
  • Endothelium, Vascular* / metabolism
  • Endothelium, Vascular* / physiology
  • Epoprostenol / biosynthesis
  • Glucocorticoids / physiology*
  • Humans
  • Hydrocortisone / pharmacology
  • Isoenzymes / physiology
  • Muscle, Smooth, Vascular* / drug effects
  • Muscle, Smooth, Vascular* / metabolism
  • Muscle, Smooth, Vascular* / physiology
  • Nitric Oxide Synthase / biosynthesis*
  • Receptors, Glucocorticoid / drug effects
  • Vasoconstriction / drug effects

Substances

  • Glucocorticoids
  • Isoenzymes
  • Receptors, Glucocorticoid
  • Epoprostenol
  • 11-beta-Hydroxysteroid Dehydrogenases
  • Nitric Oxide Synthase
  • Hydrocortisone