1. 11β-Hydroxysteroid dehydrogenase converts cortisol to inactive cortisone in man. In distal renal tubules, this inactivation protects mineralocorticoid receptors from cortisol. Congenital 11β-hydroxysteroid dehydrogenase deficiency and inhibition of 11β-hydroxysteroid dehydrogenase by liquorice or carbenoxolone result in cortisol-dependent hypokalaemia and hypertension.
2. 11β-Hydroxysteroid dehydrogenase is expressed in vascular smooth muscle. Both glucocorticoids and mineralocorticoids potentiate vascular responses to noradrenaline. 11β-Hydroxysteroid dehydrogenase activity may therefore influence vascular tone.
3. Experiments were performed in healthy subjects with and without 7 days of oral administration of 11β-hydroxysteroid dehydrogenase inhibitors (liquorice or carbenoxolone), and in a patient with congenital 11β-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 11β-hydroxysteroid dehydrogenase deficiency (87 units). In congenital 11β-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 11β-hydroxysteroid dehydrogenase modulates the access of cortisol to vascular receptors and thereby influences vascular sensitivity to noradrenaline. Complementary to its role in kidney, 11β-hydroxysteroid dehydrogenase could influence blood pressure by this mechanism, which may underlie our observations of impairment of 11β-hydroxysteroid dehydrogenase and increased dermal vascular sensitivity to cortisol in patients with essential hypertension.