Effects of the thromboxane-receptor antagonists AH 23848 and BM 13.177 on human uteroplacental arteries.
OBJECTIVE
We studied the effects of the thromboxane (Tx)A2-receptor antagonists AH 23848 and BM 13.177 in small isolated human uteroplacental arteries.


METHODS
Fetal stem villous arteries and maternal intramyometrial arteries were dissected from placental specimens and from myometrial biopsies obtained at cesarean or from nonpregnant women after hysterectomy. Vascular ring preparations were prepared and mounted in organ baths, and isometric tension was recorded.


RESULTS
AH 23848 produced competitive, concentration-dependent inhibition of responses to the TxA2-mimic U46619 in all vessel types tested. Mean (+/- standard error of the mean) pA2 values (the negative logarithm of the concentration of antagonist needed to double the half maximum response [EC50] value for U46619) were 8.69 +/- 0.16 in the stem villous arteries, 9.58 +/- 0.33 in intramyometrial arteries from term pregnant women, and 9.25 +/- 0.47 in intramyometrial arteries from nonpregnant women. In stem villous arteries, the pA2 value for BM 13.177 was 6.15 +/- 0.13, whereas these values in intramyometrial arteries could not be assessed. However, the concentrations needed to produce inhibition of U46619-induced contractions were considerably higher for BM 13.177 than for AH 23848. Both drugs inhibited responses to prostaglandin (PG)F2 alpha and PGE2 in stem villous arteries, while leaving responses to vasopressin in intramyometrial arteries unaffected. No differences in the effects of the two antagonists were found between intramyometrial arteries from nonpregnant and term pregnant women.


CONCLUSIONS
Our results suggest that TxA2-receptor antagonists effectively inhibit responses to TxA2 in human uteroplacental arteries, and such drugs may represent an interesting therapeutic approach in preeclampsia.
Svane
D
D
Department of Obstetrics and Gynecology, University of Aarhus, Denmark.
Skajaa
K
K
Andersson
K E
KE
Forman
A
A
D000328:Adult; D001158:Arteries / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D017482:Receptors, Thromboxane; D013449:Sulfonamides / Q000494:pharmacology*; D013931:Thromboxanes / Q000037:antagonists & inhibitors*; D014599:Uterus / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology
D001713:Biphenyl Compounds; D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D013931:Thromboxanes; D014667:Vasopressins; C040624:sulotroban; C046926:AH 23848; D015237:Dinoprost; D015232:Dinoprostone