Inhibition of cyclooxygenase but not nitric oxide synthase influences effects on the human omental artery of the thromboxane A(2) mimetic U46619 and 17 beta-estradiol

OBJECTIVE: These experiments were performed to study the influence of endot helial factors on the contractile effect of the thromboxane A(2) analog U46 619 and on the relaxant action of 17 beta -estradiol on isolated human omen tal arteries from nonpregnant women, women with normal pregnancies, and wom en with preeclampsia. STUDY DESIGN: Arterial rings (3 mm) with or without endothelium were suspen ded in organ chambers filled with Krebs buffer, 37 degreesC, aerated with 5 % carbon dioxide in air, pH approximately 7.4, for isometric tension record ing. Rings were incubated with indomethacin, N-omega-nitro-L-arginine, or 1 7p-estradiol, alone or in combination. The concentration that produced 50% of maximal effect, the area under the curve, and the maximal effect of U466 19, normalized with respect to a reference contraction in response to potas sium chloride, were compared. RESULTS: Neither indomethacin nor N-omega-nitro-L-arginine changed the basa l tone of omental artery rings. Neither Nw-nitro-L-arginine nor removal of the endothelium affected either the contractile action of U46619 or the rel axant action of 17p-estradiol. In contrast, indomethacin potentiated the co ntractile effect of U46619 and abolished the inhibitory effect of 17p-estra diol in rings from all three groups. The effects of U46619 and 17 beta -est radiol were significantly less in rings from women with normal pregnancy th an in those from women with preeclampsia. Tissues from women with preeclamp sia demonstrated the highest contractile response to U46619. CONCLUSION: The inhibitory effect of 17 beta -estradiol is not due to incre ased production of endothelial nitric oxide but rather involves inhibitory products of the cyclooxygenase pathway, The effect of indomethacin may resu lt from inhibited production or release of eicosanoids or from sensitizatio n of thromboxane A(2) receptors.