Glucocorticoids and blood pressure: a role for the cortisol/cortisone shuttle in the control of vascular tone in man.
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)
Walker
B R
BR
University of Edinburgh, Department of Medicine, Western General Hospital, Scotland, U.K.
Connacher
A A
AA
Webb
D J
DJ
Edwards
C R
CR
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000328:Adult; D001794:Blood Pressure / Q000502:physiology*; D002229:Carbenoxolone / Q000494:pharmacology; D003348:Cortisone / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000502:physiology*; D006035:Glycyrrhiza; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000172:deficiency; D007668:Kidney / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D010946:Plants, Medicinal; D012867:Skin / Q000098:blood supply; D014661:Vasoconstriction / Q000187:drug effects
D005938:Glucocorticoids; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D002229:Carbenoxolone; D003348:Cortisone; D006854:Hydrocortisone; D009638:Norepinephrine