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Article Review/Hyperlink
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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)
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