New mineralcorticoids in the syndrome of low-renin essential hypertension

Abstract

Patients with low-renin essential hypertension have certain features consistent with excessive mineralocorticoid activity. Because known mineralocorticoids are normal in the majority of low-renin essential hypertension patients, an unknown mineralocorticoid was sought in the urine of such patients. Using adrenalectomized rats to assay mineralocorticoids, urine extracts from patients with low-renin essential hypertension were found to contain more mineralocorticoid activity than could be accounted for by the known mineralocorticoids in the extract. The substances causing this unexplained mineralocorticoid activity were purified and then identified by mass spectral analysis as 16β-hydroxydehydroepiandrosterone (16/gb-OH-DHEA) and its 16-oxo-17β-ol isomer. That these steroids are in fact mineralocorticoids was confirmed by demonstrating that the synthetic compounds have mineralocorticoid potency l/40th that of aldosterone in the rat bioassay. Also, the mineralocorticoid effects of both the urine extracts and the synthetic steroids were blocked in the rat by spironolactone, a mineralocorticoid antagonist. The new mineralocorticoids appear to have clinical significance since they appeared in the urine in abnormally large quantities in 15 out of 15 patients with low-renin essential hypertension but only one out of 14 patients with hypertension and normal or high plasma renin activity.