Direct vascular effects of 19-hydroxyandrostenedione.
A C19 steroid, 19-hydroxyandrostenedione (19-OHAD), an amplifier of the mineralocorticoid effects of aldosterone, is known to cause hypertension in rats during chronic administration. In the present study we examined the direct vasoconstrictive effects of 19-OHAD and aldosterone in vitro as a possible mechanism of their hypertensinogenic effects. Contractile responses of central ear arteries from normal male rabbits to either 19-OHAD or aldosterone were examined in Krebs' bicarbonate buffer. When given alone, neither 19-OHAD nor aldosterone consistently caused contraction of the arteries, nor did 19-OHAD amplify the contractile action of aldosterone to a detectable range. Pretreatment of the ear arteries with desipramine, an inhibitor of neuronal uptake (uptake 1) of norepinephrine (NE), resulted in significant concentration-dependent contraction by each steroid. This contraction was markedly attenuated by prazosin but not by yohimbine. Both steroids significantly potentiated the contractile reaction of the ear arteries to exogenous NE in a dose-related manner without pretreatment with desipramine, suggesting that 19-OHAD may increase vascular resistance through the inhibition of extraneuronal NE uptake (uptake 2). These results suggest that 19-OHAD is not an amplifier of aldosterone at the vascular site.
Department of Geriatric Medicine, Osaka University Medical School, Japan.
H
H
Mikami
T
T
Ogihara
H
H
Ohde
K
K
Katahira
K
K
Kohara
Y
Y
Kumahara
D000450:Aldosterone / Q000494:pharmacology; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004423:Ear / Q000098:blood supply; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D013148:Spironolactone / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D013148:Spironolactone; D000735:Androstenedione; D000450:Aldosterone; C011482:19-hydroxy-4-androstene-3,17-dione; D003891:Desipramine; D009638:Norepinephrine; D011224:Prazosin