Current Vascular Pharmacology

Dimitri P. Mikhailidis  
Academic Head, Deptartment of Clinical Biochemistry
Royal Free Hospital Campus
University College London Medical School
University College London (UCL)
Pond Street
London, NW3 2QG
UK

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Glucocorticoids and Vascular Reactivity

Author(s): Shumei Yang, Lubo Zhang.

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 β-hydr oxysteroid de hydrogenase (11β-HSD ). The presence of 11β-HSD in many tissue s suggests that it modulates the access of corticosteroids to the irreceptors at both renal and extra-renal sites. The two 11β-HSD isozyme scatalyze the inte rconversion of cortisol and cortisone . Type 1 11β-HSD has bidirec tiona l activity, while the type 2 mainly conver ts cortisol into cor tisone, the biologically inactive form. Both type 1 and type 2 11β-HSD have been found in vascular e ndothelial and smooth muscle c ells, suggesting that a bnormal 11β- HSD expression may play a pathoge nicrole in the common forms of hypertension. In this a rticle, we review possible mechanisms involved in the glucocorticoid-mediated potentiation of vascular reactivity, its regulation by 11β-HSD , and their physiological and pathophysiologica l significance.

Keywords: glucocorticoids, hydroxysteroid dehydrogenase, vascular smooth muscle, endothelium, nitric oxide, prostacyclin, pharmacomechanical coupling

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Article Details

VOLUME: 2
ISSUE: 1
Year: 2004
Page: [1 - 12]
Pages: 12
DOI: 10.2174/1570161043476483