Why eicosanoids could represent a new class of tocolytics on uterine activity in pregnant women.
OBJECTIVE
The purpose of this study was to assess the effects of exogenous eicosanoids on spontaneous uterine contractile activity.


METHODS
Eight uterine biopsies were performed from women who were undergoing elective cesarean delivery. Tension measurements were performed in vitro on myometrial strips. Contractile activities were quantified by the calculation of the area under the curve. The effects of eicosanoids and specific enzyme inhibitors were assessed. Fractions from various uterine tissues were analyzed by Western blot.


RESULTS
Data demonstrate the presence, in some tested tissues, of cytochrome P-450 epoxygenase and soluble epoxide hydrolase, which respectively produce and degrade epoxyeicosatrienoic acid regioisomers. Inhibition of soluble epoxide hydrolase with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid or omega-hydroxylase with N-methylsulfonyl-12,12-dibromododec-11-enamide resulted in a tocolytic effect; N-methylsulfonyl-6-[2-propargyloxyphenyl] hexanamide, which is an epoxygenase inhibitor, had no effect. Exogenous epoxyeicosatrienoic acids displayed significant tocolytic effects on spontaneous contractile activities.


CONCLUSIONS
Epoxy- and hydroxyeicosanoids represent new bioactive, arachidonic acid by-products with in vitro tocolytic activities. These findings suggest that cytochrome P-450 isozymes may represent relevant pharmacologic targets under physiopathologic conditions.
Department of Obstetrics and Gynecology, Université de Sherbrooke, Sherbrooke, QC, Canada.
Stéphanie
S
Corriveau
Maryse
M
Berthiaume
Eric
E
Rousseau
Jean-Charles
JC
Pasquier
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D015153:Blotting, Western; D015777:Eicosanoids / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D011247:Pregnancy; D013718:Tensile Strength; D015149:Tocolytic Agents / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*; D055815:Young Adult
D015777:Eicosanoids; D015149:Tocolytic Agents