Glycyrrhetinic acid attenuates vascular smooth muscle vasodilatory function in healthy humans

Piotr Sobieszczyk, Barry A Borlaug, Heather L. Gornik, Wesley D. Knauft, Joshua A. Beckman

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Abnormal glucocorticoid metabolism contributes to vascular dysfunction and cardiovascular disease. Cortisol activation of vascular mineralocorticoid and glucocorticoid receptors is regulated by two types of 11β-HSD (11-β hydroxysteroid dehydrogenase), namely 11β-HSD2 and 11β-HSD1 (type 2 and type 1 11β-HSD respectively). We hypothesized that inhibition of 11β-HSD would attenuate vascular function in healthy humans. A total of 15 healthy subjects were treated with the selective 11β-HSD inhibitor GA (glycyrrhetinic acid) or matching placebo in a randomized double-blinded cross-over trial. 11β-HSD activity was assessed by the urinary cortisol/cortisone ratio, and vascular function was measured using strain-gauge plethysmography. Endothelial function was measured through incremental brachial artery administration of methacholine (0.3-10 μg/min) and vascular smooth muscle function with incremental verapamil (10-300 μg/min). GA increased the 24-h urinary cortisol/cortisone ratio compared with placebo (P = 0.008). GA tended to reduce the FBF (forearm blood flow) response to methacholine (P = 0.09) and significantly reduced the FBF response to verapamil compared with placebo (P = 0.04). MAP (mean arterial pressure) did not differ between the study conditions. 11β-HSD inhibition attenuated vascular smooth muscle vasodilatory function in healthy humans. Disturbances in cortisol activity resulting from 11β-HSD inactivation is therefore a second plausible mechanism for mineralocorticoid-mediated hypertension in humans.

Original languageEnglish (US)
Pages (from-to)437-442
Number of pages6
JournalClinical Science
Volume119
Issue number10
DOIs
StatePublished - Nov 2010
Externally publishedYes

Fingerprint

Glycyrrhetinic Acid
11-beta-Hydroxysteroid Dehydrogenases
Vascular Smooth Muscle
Hydrocortisone
Blood Vessels
Methacholine Chloride
Cortisone
Placebos
Verapamil
Forearm
Mineralocorticoid Receptors
Mineralocorticoids
Plethysmography
Brachial Artery
Glucocorticoid Receptors
Vascular Diseases
Cross-Over Studies
Glucocorticoids
Healthy Volunteers
Arterial Pressure

Keywords

  • 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2)
  • Glycyrrhetinic acid
  • Hypertension
  • Mineralocorticoid receptor
  • Vascular function
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Glycyrrhetinic acid attenuates vascular smooth muscle vasodilatory function in healthy humans. / Sobieszczyk, Piotr; Borlaug, Barry A; Gornik, Heather L.; Knauft, Wesley D.; Beckman, Joshua A.

In: Clinical Science, Vol. 119, No. 10, 11.2010, p. 437-442.

Research output: Contribution to journalArticle

Sobieszczyk, Piotr ; Borlaug, Barry A ; Gornik, Heather L. ; Knauft, Wesley D. ; Beckman, Joshua A. / Glycyrrhetinic acid attenuates vascular smooth muscle vasodilatory function in healthy humans. In: Clinical Science. 2010 ; Vol. 119, No. 10. pp. 437-442.
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