A reevaluation of the mineralocorticoid and hypertensinogenic potential of 19-hydroxyandrostenedione.
Experiments were done to evaluate whether 19-hydroxyandrostenedione (19-OH-A) is a steroid which produces hypertension and amplifies the mineralocorticoid effects of aldosterone. No intrinsic mineralocorticoid or adosterone-amplifying effect was found in several bioassays using adrenalectomized rats at doses of 100 micrograms 19-OH-A and/or 0.1 microgram aldosterone or in assays in which urine electrolytes were measured daily during a 14-day continuous infusion of 100 micrograms/day 19-OH-A. In two different experiments, the twice weekly administration of 0.1-1 mg 19-OH-A in oil to intact rats' drinking water failed to produce a change in blood pressure after 6 weeks. When one kidney was removed from these rats and 0.9% saline was substituted for drinking water, the blood pressures of rats receiving 1 mg twice weekly of 19-OH-A became significantly elevated in only one of the two experiments. At the end of 10 weeks, the average 19-OH-A pressure (139 mmHg) was significantly (P less than 0.01) greater than average control pressure (114 mmHg), but significantly (P less than 0.01) less than the mean average pressure of rats receiving 5 mg deoxycorticosterone acetate (DOCA) (161 mmHg). In another experiment uninephrectomized rats received 0.5 mg 19-OH-A or 1 mg DOCA 3 times a week. After 5 weeks the pressure of those receiving 19-OH-A was 149 mmHg, significantly greater (P less than 0.01) than controls (123 mmHg), but significantly less (P less than 0.01) than that of those rats receiving DOCA (189 mmHg). Our data failed to confirm the aldosterone amplifying effect of 19-OH-A. We did obtain a small elevation of arterial pressure in unilaterally nephrectomized rats receiving saline to drink. The differences between our results and those reported for this compound are not readily apparent, but may be related to genetic differences within the Sprague-Dawley strain used in both studies and/or to diet.
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D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology*; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001681:Biological Assay; D001794:Blood Pressure / Q000187:drug effects*; D003900:Desoxycorticosterone / Q000494:pharmacology; D004347:Drug Interactions; D008297:Male; D009392:Nephrectomy; D011188:Potassium / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine
D000735:Androstenedione; D003900:Desoxycorticosterone; D000450:Aldosterone; D012964:Sodium; C011482:19-hydroxy-4-androstene-3,17-dione; D011188:Potassium