Abstract
The mineralocorticoid activities and effects on blood pressure of synthetic 16 (βdihydroxy-5-androsten-17-one) and its isomer, 16-oxo-A (16-oxo-androstenediol, 3β, 17β- dihydroxy-5-androsten-16-one) were examined in rats. In study 1, three groups of 5 rats each were given subcutaneous injections of 0.2 ml of ethanolic solutions for 4 weeks. Their drinking water contained 1% NaCl. In group I, the control group, 20% ethanol was injected.Each rat at in group II was given a daily injection of 20% ethanol containing 400pg of 16β- OH-DHEA. Each rat in group III was given a daily injection of 400 μg of 16-oxo-A in 20% ethanol. Body weight and systolic blood pressure were monitored twice weekly. The urinary Na+/K+ ratio was determined on the 14th and 29th days. Serum Na+, K+, and hematocrit analyses were done on the 29th day. Plasma renin activity was assayed in samples obtained before and after furosemide administration on the 29th and 30th days, respectively. There were no significant differences in the mean values of any of the determinations listed above between groups II and III (treated) and group I (control) with one exception. The mean hematocrit of group II was slightly (4%) but significantly (P<0.01) less than that of the control group on the 29th day.
In study 2, unilaterally nephrectomized salt loaded male Wistar rats were injected once a week with large doses of steroids in sesame oil for 2 month periods. Rats injected with 10 mg and with 30 mg of 11-desoxycorticosterone acetate per kg of body weight per week developed hyertension. Rats given 30 mg/kg BW/week of 16β-OH-DHEA or 16-oxo-A and control rats did not develop hypertension.
Other investigators have postulated that 16β-OH-DHEA and possibly its 16-oxo isomer are direct causative factors in the pathogenesis of low renin hypertension in humans. In contrast, we have not been able to demonstrate any substantial minerolocorticoid activity or any effect on blood pressure for either of these steroids. We conclude that it is unlikely that 16β-OH-DHEA and 16-oxo-A are direct causative factors in the production of low renin essential hypertension. On the other hand, if 16β-OH-DHEA is excreted in abnormally large amounts in the urine of patients with low renin hypertension, it may be a maker of the disease even if it is not a direct causative factor.
