HDCN Article Review/Hyperlink

Takeda Y, Miyamori I, Iki K, Inaba S, Furukawa K, et al.

Endogenous renal 11ß-hydroxysteroid dehydrogenase inhibitory factors in essential hypertension

Hypertension (Feb) 27:197-201 1996

For original abstract, click here.
11-ß-hydroxysteroid dehydrogenase (11-ß-HSD) catalyzes conversion of glucocorticoids to inactive metabolites. If this enzyme is deficient, (deficiency can be induced by licorice or carbenoxolone ingestion), sodium retention and hypertension supervene, because the resultant high local levels of glucocorticoids can activate mineralocorticoid receptors in the kidney. Endogenous inhibitors of 11-ß-HSD have been found in the urine. It has long been speculated, but never proven, that low-renin hypertensives may have increased mineralocorticoid activity. In the present study, urinary excretion of a panel of steroid hormones, as well as inhibitory factors of the 11-ß-HSD enzyme were compared in 30 Japanese patients with low-renin hypertension vs. 20 controls.

Urinary excretion of 11-ß-HSD inhibitory factor was higher (1280 nmol/d)) in low-renin hypertensives than in controls (704 nmol/d), although the ratio of cortisol metabolites to cortisol was similar in the two groups. The excretion of inhibitory factor correlated with urinary sodium excretion. Salt restriction substantially reduced urinary excretion of 11-ß-HSD inhibitory factor in normotensives, suggesting the sodium, via a hormonal pathway, may modulate activity in this enzyme.

Comment: The authors cite studies in Dahl salt-sensitive rats, where activity of 11-ß-HSD is reduced, rather than increased. Other studies cited show normal or increased ratios of cortisol to metabolites in the urine of low-renin hypertensives. In one study sited, the half-life of radio-labelled cortisol was increased in hypertensive subjects. Whether an excess of endogenous inhibitory factors of cortisol metabolism contribute to of low-renin hypertension remains a fascinating, and as yet unanswered, question. (John T. Daugirdas, M.D., University of Illinois at Chicago)