Sensitivity to the thromboxane A2 analog U46619 varies with inner diameter in human stem villous arteries

• Size-dependent reduction in sensitivity to U46619 in stem villous arteries.
• TxA2 may not be as critical for placental resistance as previously expected.
• Low TxA2 reactivity may explain the clinical failure of TxA2 inhibition.
• Care must be taken with experimental studies on stem villous arteries using U46619.

IntroductionThe vascular resistance of stem villous arteries is determined by the balance between different contractile and relaxant agents and in the utero-placental circulation. Thromboxane A2 (TxA2), prostaglandin F2α (PGF2α) and endothelin-1 (ET-1) are considered to be among the most important contractile factors. However, it is not known if their contractile effects are consistent along the villous tree. We hypothesized that the sensitivity to different agonists could be influenced by artery diameter and thus that their contribution to placental vascular resistance may differ.MethodsUsing an isometric wire myograph, the contractility and sensitivity (pD2) to the thromboxane A2 mimetic U46619, PGF2α and ET-1 were investigated in isolated human stem villous arteries and human uterine fundus and isthmus arteries obtained from healthy, pregnant women who had experienced uncomplicated pregnancy.ResultsIn fetal arteries, the pD2 values for U46619 correlated positively with arterial diameter with no such dependence observed for ET-1 and PGF2α. In maternal arteries, pD2 remained constant for all the agonists tested despite highly variable vessel diameter.DiscussionA selective decrease in sensitivity to TxA2 receptor stimulation was observed with decreasing vascular diameter in human stem villous arteries. The contractile factors PGF2α and ET-1 show no such relationship.