19-Hydroxyandrostenedione amplifies the hypertensive action of mineralocorticoids in rats.
We have reported that 19-hydroxyandrostenedione (19-OH-A-dione) amplifies the sodium-retaining action of aldosterone. To evaluate whether it also amplifies the hypertensive action of small doses of aldosterone, mononephrectomized rats were given 0.5 mg aldosterone, 10 mg 19-OH-A-dione or a combination of both once a week for 19 weeks, and changes in blood pressure were evaluated. Rats were given 154 mmol NaCl/l to drink. The blood pressure of controls, rats given aldosterone alone, 19-OH-A-dione alone or a combination of both in week 19 were 137 +/- 4 (S.E.M.), 146 +/- 7, 147 +/- 4 and 191 +/- 8 mmHg respectively. The blood pressure of rats given the combination was significantly higher than any of the other three groups. These results indicate that 19-OH-A-dione amplifies the hypertensive action of aldosterone and may be considered a potent hypertensive agent in the presence of aldosterone. To evaluate whether 19-OH-A-dione amplifies the hypertensive action of small doses of deoxycorticosterone acetate (DOCA), another experiment was carried out in which similar rats were given 5 mg DOCA or a combination of 5 mg DOCA and 10 mg 19-OH-A-dione once a week for 8 weeks. The blood pressure of controls, rats given DOCA alone and a combination of DOCA and 19-OH-A-dione in week 8 were 139 +/- 5, 166 +/- 7 and 208 +/- 12 mmHg respectively. The blood pressure of rats given a combination of DOCA and 19-OH-A-dione was significantly higher than that of control rats or the rats given DOCA alone. These results indicate that 19-OH-A-dione can also amplify the hypertensive action of DOCA. It is concluded that 19-OH-A-dione amplifies the hypertensive action of mineralocorticoids as well as the sodium-retaining action of aldosterone.
Third Department of Internal Medicine, University of Tokyo Faculty of Medicine, Japan.
H
H
Sekihara
Y
Y
Yazaki
T
T
Kojima
D000450:Aldosterone / Q000494:pharmacology; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003900:Desoxycorticosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008901:Mineralocorticoids / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008901:Mineralocorticoids; D000735:Androstenedione; D003900:Desoxycorticosterone; D000450:Aldosterone; C011482:19-hydroxy-4-androstene-3,17-dione