OBJECTIVE: 11 beta-Hydroxysteroid dehydrogenase protects renal mineralocorticoid receptors from cortisol by converting cortisol to inactive cortisone. 11 beta-Dehydrogenase deficiency, either congenital or after inhibition by liquorice and carbenoxolone, results in cortisol-dependent mineralocorticoid excess and hypertension. We tested the hypothesis that the same mechanism occurs in some patients with essential hypertension. DESIGN/PATIENTS: Twenty patients with essential hypertension were compared with 19 matched healthy controls. MEASUREMENTS: 11 beta-Hydroxysteroid dehydrogenase activity was assessed by the half-life of 11 alpha-3H-cortisol, and by the ratios of cortisol to cortisone in plasma and of their metabolites in urine. Renal mineralocorticoid receptor activation was assessed by plasma potassium, renin activity and aldosterone. RESULTS: Half-lives of 11 alpha-3H-cortisol were prolonged in a subgroup of hypertensives (mean +/- SE 53.2 +/- 3.6 min in hypertensives 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 cortisone in plasma and of their metabolites in urine were not different. 11 alpha-3H-Cortisol half-lives correlated with blood pressure but not with indices of renal mineralocorticoid receptor activation. CONCLUSIONS: 11 beta-Dehydrogenase is defective in a proportion of patients with essential hypertension. The normal ratios of cortisol to cortisone in plasma and of their metabolites in urine, also seen after carbenoxolone administration, suggest that 11 beta-reductase conversion of cortisone to cortisol is also defective. Unlike other syndromes of 11 beta-dehydrogenase deficiency, the defect was not associated with mineralocorticoid excess. We suggest that it may cause hypertension by increasing exposure of vascular steroid receptors to cortisol.
OBJECTIVE: 11 beta-Hydroxysteroid dehydrogenase protects renal mineralocorticoid receptors from cortisol by converting cortisol to inactive cortisone. 11 beta-Dehydrogenase deficiency, either congenital or after inhibition by liquorice and carbenoxolone, results in cortisol-dependent mineralocorticoid excess and hypertension. We tested the hypothesis that the same mechanism occurs in some patients with essential hypertension. DESIGN/PATIENTS: Twenty patients with essential hypertension were compared with 19 matched healthy controls. MEASUREMENTS: 11 beta-Hydroxysteroid dehydrogenase activity was assessed by the half-life of 11 alpha-3H-cortisol, and by the ratios of cortisol to cortisone in plasma and of their metabolites in urine. Renal mineralocorticoid receptor activation was assessed by plasma potassium, renin activity and aldosterone. RESULTS: Half-lives of 11 alpha-3H-cortisol were prolonged in a subgroup of hypertensives (mean +/- SE 53.2 +/- 3.6 min in hypertensives 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 cortisone in plasma and of their metabolites in urine were not different. 11 alpha-3H-Cortisol half-lives correlated with blood pressure but not with indices of renal mineralocorticoid receptor activation. CONCLUSIONS: 11 beta-Dehydrogenase is defective in a proportion of patients with essential hypertension. The normal ratios of cortisol to cortisone in plasma and of their metabolites in urine, also seen after carbenoxolone administration, suggest that 11 beta-reductase conversion of cortisone to cortisol is also defective. Unlike other syndromes of 11 beta-dehydrogenase deficiency, the defect was not associated with mineralocorticoid excess. We suggest that it may cause hypertension by increasing exposure of vascular steroid receptors to cortisol.
Authors: Abdulmaged M Traish; Roberto Cosimo Melcangi; Marco Bortolato; Luis M Garcia-Segura; Michael Zitzmann Journal: Rev Endocr Metab Disord Date: 2015-09 Impact factor: 6.514
Authors: Pablo Stiefel; José S García-Morillo; Luis Jimenez; Encarnación Pamies; María Luisa Miranda; Joaquín Carneado; José Villar; Alfonso Leal-Cerro Journal: Endocrine Date: 2002-08 Impact factor: 3.633
Authors: Lama Ghazi; Tanja Dudenbostel; Maria El Hachem; Mohammed Siddiqui; Chee Paul Lin; Suzanne Oparil; David A Calhoun Journal: Am J Hypertens Date: 2017-05-01 Impact factor: 2.689