Mechanisms of Endothelium-Dependent Relaxation in Myometrial Resistance Vessels and Their Alteration in Preeclampsia

Abstract

Objective: To investigate the importance of prostacyclin and nitric oxide synthesis in endothelium-dependent relaxation in myometrial resistance vessels, and to test the hypothesis that a deficiency in nitric oxide synthesis contributes to the known alterations in endothelial function in preeclampsia.Methods: Thirty-six women with normal pregnancies and 14 with preeclampsia had the myometrium biopsied at cesarean section. Resistance arteries were dissected and mounted on a wire myograph. After preconstriction with vasopressin, vessels were treated cumulatively with bradykinin. The process was repeated in the presence of indomethacin and then indomethacin and NG-monomethyl-L-arginine (L-NMMA).Results: The vessels from women with normal pregnancies showed endothelium-dependent relaxation to bradykinin which was not significantly altered by the presence of indomethacin. The addition of L-NMMA significantly, but only partially, reduced the relaxation to bradykinin in the presence of indomethacin (p= 0.03).The vessels from women with preeclampsia showed markedly reduced relaxation to bradykinin (p < 0.0001), as compared to vessels from normal pregnant women. Relaxation of vessels from women with preeclampsia was increased by the addition of indomethacin (p = 0.03) but was virtually eradicated by the presence of L-NMMA.Conclusions: Eicosanoid synthesis plays little part in the relaxation of normal pregnant myometrial vessels to bradykinin. Nitric oxide synthesis mediates part but not all of the endothelium-dependent relaxation. In preeclampsia, relaxation to bradykinin is reduced; inhibition of eicosanoid synthesis allows increased relaxation, and nitric oxide synthesis appears to mediate a greater proportion of the relaxation than in normal pregnant women.