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Anesthesia & Analgesia, Vol 82, 288-293, Copyright © 1996 by International Anesthesia Research Society
Pregnancy and ephedrine increase the release of nitric oxide in ovine uterine arteries
P Li, C Tong and JC Eisenach
Department of Anesthesia, Wake Forest University Medical Center, Winston-Salem, North Carolina 27157-1009, USA.
Ephedrine is the preferred vasoconstrictor for the treatment of hypotension
after epidural and spinal anesthesia in obstetrics because it preserves
uterine perfusion better than pure alpha-adrenergic agonists. Previous
studies of uterine vascular rings in vitro suggested that direct uterine
vasoconstriction from ephedrine is reduced during pregnancy. This study
examined the hypothesis that nitric oxide synthase (NOS) is up-regulated in
uterine arteries during pregnancy, and that ephedrine stimulates NOS to
release nitric oxide (NO) and diminish direct vasoconstriction. Uterine
arterial vessels were obtained from 12 pregnant and 9 nonpregnant ewes, and
vessel tension was monitored in vitro in response to escalating
concentrations of ephedrine or metaraminol. In some experiments, vascular
endothelium was mechanically removed, while in others antagonists of NO
synthesis (N omega-nitro-L-arginine methyl ester [L-NAME], NO diffusion
(hemoglobin [Hgb]), or guanylate cyclase (methylene blue [MB]) were
included. In other experiments, solutions containing ephedrine were
superfused over uterine arteries from pregnant ewes onto uterine arteries
from nonpregnant ewes. Finally, NOS activity, determined by 14C-citrulline
generation, was determined in uterine arteries from pregnant and
nonpregnant ewes. Both ephedrine and metaraminol caused concentration-
dependent constriction of uterine arterial rings from pregnant and
nonpregnant animals. Pregnancy reduced maximum constriction from ephedrine
more than metaraminol. Similarly, ephedrine-induced constriction was
increased more than that of metaraminol in uterine arteries from pregnant
animals treated to diminish the effects of nitric oxide (L-NAME, Hgb, MB,
endothelium removal). Ephedrine's constriction of uterine arteries from
nonpregnant animals was reduced when it was superfused over uterine
arteries from pregnant animals. NOS activity was increased in uterine
arteries from pregnant compared to nonpregnant animals. These studies
confirm decreased direct uterine arterial vasoconstriction during pregnancy
from ephedrine and support the hypothesis of increased release of an
endogenous vasodilator (NO), either from the vascular endothelium or the
vessel wall, as the cause for this decreased vasoconstriction.
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