8
Views
1
CrossRef citations to date
0
Altmetric
Original Article

Effects of Thromboxane Synthase Inhibition on Placental Prostacyclin and Thromboxane Production

Pages 1-18 | Published online: 07 Jul 2009
 

Abstract

Selective inhibition of thromboxane synthesis without affecting prostacyclin synthesis is being considered as a potential treatment for preeclampsia because of its imbalance of increased thromboxane/decreased prostacyclin production. Thromboxane production by the placenta is greatly increased in preeclampsia so effective therapy must inhibit placental, as well as maternal platelet, thromboxane production. The following study was done to evaluate the production rates of thromboxane and prostacyclin in placental tissues incubated with and without the throraboxane synthase inhibitor, U-63,557A. Fresh, human term placental tissues (350 mg) were incubated in a sterile manner in 7 ml Dulbecco's Modified Eagle's Medium for 48 hours at 37°C with 95% oxygen and 5% carbon dioxide in a metabolic shaker. Samples were collected at 0, 8, 20, 32 and 48 hours and analyzed for thromboxane A2 by radioimmunoassay of its stable metabolite, thromboxane B2, and for prostacyclin by radioimmunoassay of its stable metabolite, 6-keto prostaglandin F1a. Addition of U-63,557A, 0.1 μM, significantly decreased (P < 0.001) thromboxane production in both preeclamptic (n=6) and normal placentas (n=5). Placental prostacyclin production was not affected (P>0.6) by addition of U-63,557A in either normal or preeclamptic placentas. The placental production rate ratios of thromboxane to prostacyclin were significantly higher for preeclampsia than for normal pregnancy, and addition of U-63,557A to preeclamptic tissue reduced the thromboxane/prostacyclin ratios to those of normal placental tissue. Therefore, inhibition of placental thromboxane synthase results in selective inhibition of thromboxane synthesis without affecting placental prostacyclin synthesis, and it can restore the increased ratio of thromboxane to prostacyclin of preeclampsia to that of normal pregnancy.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.