Enhancement of the hypertensinogenic action of 19-hydroxyandrostenedione by aromatase inhibitor, delta 1-testololactone.
To evaluate the enhancing effects of 1,2-dehydrotestololactone (delta 1-testololactone) on the hypertensinogenic action of 19-hydroxyandrostenedione (19-OH-A-dione), 1 mg 19-OH-A-dione, 10 mg delta 1-testololactone, or a combination of 1 mg 19-OH-A-dione and 10 mg delta 1-testololactone was injected into intact rats drinking water once a week for 4 weeks. The blood pressure of control rats and rats given 19-OH-A-dione, delta 1-testololactone, and a combination of 19-OH-A-dione and delta 1-testololactone in the fourth week was 130 +/- 2 (SE), 140 +/- 2, 128 +/- 6, and 152 +/- 5 mmHg, respectively. The blood pressure of rats given 19-OH-A-dione and a combination of 19-OH-A-dione and delta 1-testololactone was significantly higher than that of control rats. In addition, the blood pressure of rats given a combination of 19-OH-A-dione and delta 1-testololactone was significantly higher than that of rats given 19-OH-A-dione alone. As delta 1-testololactone itself did not show any hypertensinogenic action, it is considered to enhance the hypertensinogenic action of 19-OH-A-dione. Although plasma 19-OH-A-dione concentrations of control rats and rats given delta 1-testololactone were lower than the sensitivity of RIA, those of rats given 19-OH-A-dione and a combination of 19-OH-A-dione and delta 1-testololactone were 116 +/- 3 and 222 +/- 37 pg/ml, respectively. Plasma 19-OH-A-dione concentrations of rats given a combination of 19-OH-A-dione and delta 1-testololactone were significantly higher than those of rats given 19-OH-A-dione alone. Therefore, delta 1-testololactone is considered to enhance the action of 19-OH-A-dione by increasing plasma concentrations of 19-OH-A-dione. As delta 1-testololactone is an aromatase inhibitor, the inhibition of the conversion of circulating 19-OH-A-dione to estrogens in peripheral tissues might be the cause of the elevation of plasma 19-OH-A-dione concentrations. These results indicate that aromatose inhibitors enhance the hypertensinogenic action of 19-OH-A-dione by decreasing the degradation of 19-OH-A-dione.
Sekihara
H
H
Third Department of Internal Medicine, University of Tokyo Faculty of Medicine, Japan.
Yonemitsu
K
K
Takaku
F
F
D000735:Androstenedione / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D000818:Animals; D047072:Aromatase Inhibitors; D001794:Blood Pressure / Q000187:drug effects*; D004357:Drug Synergism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013738:Testolactone / Q000494:pharmacology*
D047072:Aromatase Inhibitors; D000735:Androstenedione; D013738:Testolactone; C011482:19-hydroxy-4-androstene-3,17-dione