DEFICIENT INACTIVATION OF CORTISOL BY 11-BETA-HYDROXYSTEROID DEHYDROGENASE IN ESSENTIAL-HYPERTENSION

OBJECTIVE 11beta-Hydroxysteroid dehydrogenase protects renal mineraloc orticoid receptors from cortisol by converting cortisol to inactive co rtisone. 11beta-Dehydrogenase deficiency, either congenital or after i nhibition by liquorice and carbenoxolone, results in cortisol-dependen t mineralocorticoid excess and hypertension. We tested the hypothesis that the same mechanism occurs in some patients with essential hyperte nsion. DESIGN/PATIENTS Twenty patients with essential hypertension wer e compared with 19 matched healthy controls. MEASUREMENTS 11beta-Hydro xysteroid dehydrogenase activity was assessed by the half-life of 11al pha-H-3-cortisol, and by the ratios of cortisol to cortisone in plasma and of their metabolites in urine. Renal mineralocorticoid receptor a ctivation was assessed by plasma potassium, renin activity and aldoste rone. RESULTS Half-lives of 11alpha-H-3-cortisol were prolonged in a s ubgroup of hypertensives (mean +/- SE 53.2 +/- 3.6 min in hypertensive s vs 42.3 +/- 2-3 in controls, P < 0.05; seven of the 20 hypertensives had half-lives exceeding 2 SD of controls). Ratios of cortisol to cor tisone in plasma and of their metabolites in urine were not different. 11alpha-H-3-Cortisol half-lives correlated with blood pressure but no t with indices of renal mineralocorticoid receptor activation. CONCLUS IONS 11beta-Dehydrogenase is defective in a proportion of patients wit h essential hypertension. The normal ratios of cortisol to cortisone i n plasma and of their metabolites in urine, also seen after carbenoxol one administration, suggest that 11beta-reductase conversion of cortis one to cortisol is also defective. Unlike other syndromes of 11beta-de hydrogenase deficiency, the defect was not associated with mineralocor ticoid excess. We suggest that it may cause hypertension by increasing exposure of vascular steroid receptors to cortisol.