The C19-mineralocorticoids in hypertension.

The excretion rates of the C19-mineralcorticoids, 16beta-hydroxy-DHEA and 16-oxo-androstenediol, were measured in subjects with low-renin essential hypertension and toxemia of pregnancy. C19-mineralocorticoid excretion in low-renin essential hypertension ranged from 70-790 microgram per day. No significant difference in 16beta-hydroxy-DHEA and 16-oxo-androstenediol excretion was found between these subjects and normal controls. Subjects with toxemia of pregnancy excreted between 350 and 2500 microgram per day of these steroids. There was no significant difference between toxemic and normal pregnancy. Thus, 16beta-hydroxy - DHEA and 16-oxo-androstenediol probably do not play an important role in either low-renin essential hypertension or toxemia of pregnancy.

Are there unknown mineralocorticoids in low-renin essential hypertension?

The blood pressure elevation of primary aldosteronism is caused by excessive production of the known mineralocorticoid, aldosterone. The blood pressure elevation of low-renin essential hypertension may also be caused by mineralocorticoid excess, but which which mineralocorticoid is responsible is uncertain. Normal levels of aldosterone, found in this disorder despite suppressed plasma renin, and the presence of an unknown mineralocorticoid have been hypothesized to explain low-renin essential hypertension. We contrasted the blood pressure responses and changes in aldosterone seen in patients with low-renin essential hypertension and primary aldosteronism during treatment with two adrenal enzyme inhibitors. The results demonstrate the similarity between decrease in blood pressure and in aldosterone during early adrenal inhibition in both primary aldosteronism and in low-renin essential hypertension. During treatment with a distal adrenal blocker, patients with primary aldosteronism demonstrated decreases in both aldosterone and blood pressure, whereas patients with low-renin essential hypertension showed a decrease in aldosterone without significant change in blood pressure. This suggested that aldosterone was not the major mineralocorticoid responsible for low-renin essential hypertension. Unknown mineralocorticoid excretion decreased (along with blood pressure) during early inhibition but failed to decrease (along with blood pressure) during late inhibition at a time when aldosterone excretion decreased. This suggests that unknown mineralocorticoids play significant roles in the blood pressure elevation of low-renin essential hypertension.

Plasma 16 beta-hydroxydehydroepiandrosterone in normal and pathological conditions in man.

Plasma 16beta-hydroxydehydroepiandrosterone (16 beta-OH-DHEA) levels in normal subjects and patients with certain pathological conditions have been evaluated using radioimmunoassay of the steroid. Plasma 16 beta-OH-DHEA levels in normal subjects rose sharply during adolescence and then declined slowly throughout adult life: 192 +/- 54 (SE) pg/ml between 7 and 11 yrs., 395 +/- 22 pg/ml between 15 and 19 yrs, 330 +/- 29 pg/ml between 20 and 39 yrs., 291 +/- 35 pg/ml between 40 and 59 yrs., and 124 +/- 20 over 60 yrs. No significant difference was found between male and female subjects. Plasma 16 beta-OH-DHEA rose significantly (P less than 0.001) during ACTH stimulation, declined significantly (P less than 0.005) during dexamethasone suppression, declined significantly (P less than 0.05) during gonadal suppression, rose significantly (P less than 0.05) during gonadal stimulation and rose significantly (P less than 0.005) after the administration of WIN 24,540, an inhibitor of 3 beta-ol-dehydrogenase. The concentration of 16 beta-OH-DHEA in adrenal venous blood was higher than in inferior vena cava blood, but 16 beta-OH-DHEA in hepatic venous blood was not higher than 16 beta-OH-DHEA in arterial blood. It is inferred that 16 beta-OH-DHEA is secreted directly by the adrenal cortex and probably the gonads. Plasma 16 beta-OH-DHEA was elevated in normal pregnant women, pregnant women with toxemia, and in patients with Cushing's disease, ectopic ACTH-producing tumor, and congenital adrenal hyperplasia, but it was not elevated in patients with low-renin essential hypertension.

PIP: Plasma 16 beta-hydroxydehydroepiandrosterone (16 beta-OH-DHEA) levels were measured by radioimmunoassay in normal and pathological conditions in man. 16 beta-OH-DHEA levels in normal subjects rose sharply during adolescence and then declined slowly throughout adult life: 192 pg/ml age 7-11, 395 pg/ml age 15-19, 330 pg/ml age 20-39, 261 pg/ml age 40-59, and 124 pg/ml over 60-years-old. No marked difference was seen between male and female subjects. 16 beta OH-DHEA rose significantly (p less than .01) during adrenocorticotropin (ACTH) stimulation, declined (p less than .005) during dexamethasome suppression and during gonadal suppression, rose (p less than .05) during gonadal stimulation and following administration of WIN 24540, an inhibitor of 3 beta-o1-dehydrogenase (p less than .005). 16 beta-OH-DHEA levels in adrenal venous blood were higher than in inferior vena cava blood but the levels in hepatic venous blood were not higher than in arterial blood. These results indicate that 16 beta-OH-DHEA is secreted directly by the adrenal cortex and probably the gonads. 16 beta-OH-DHEA levels were elevated in normal pregnant women, pregnant women with toxemia and in patients with Cushing's disease, ectopic ACTH-producing tumor and congenital adrenal hyperplasia but not in patients with low-renin essential hypertension.

Evidence for a new mineralocorticoid in patients with low-renin essential hypertension.

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. Urine extracts from patients with low-renin essential hypertension were assayed for mineralocorticoid activity in adrenalectomized rats and found to contain more such activity than could be accounted for by the known mineralocorticoids in the extracts. The factor responsible for the unexplained mineralocorticoid activity was purfied and then identified by mass spectral analysis as 16beta-hydroxydehydroepiandrosterone (16beta-OH-DHEA). Synthetic 16beta-OH-DHEA was found to have a mineralocorticoid potency one-fortieth that of aldosterone in the rat bioassay. The mineralocorticoid effects of both the urine extracts and the synthetic steroid were blocked in the rat by spironolactone, a mineralocorticoid antagonist. A specific assay for 16beta-OH-DHEA was developed, and its level in the urine was found to be elevated in patients with low-renin essential hypertension.