Endothelium-derived relaxation of canine uterine artery and arachidonic acid metabolism

Vascular responses to acetylcholine (ACh) and calcium ionophore A23187 were studied in the rings of the canine uterine arteries. Using uterine arteries of mature female mongrel dogs, ring-form specimens were prepared under a microscope. According to the Magnus' method the specimen was vertically fixed in Krebs-Henseleit solution and with a force-displacement transducer the isometric tension was determined. ACh and A23187 caused dose-dependent relaxation in the control, but it did not cause a response in endothelium-denuded preparations during contractions evoked by 3 X 10(-7)M norepinephrine. When pretreated with indomethacin (3 X 10(-6)M), a cyclooxygenase inhibitor, the maximal relaxation response induced by ACh was 73.35 +/- 14.53%, and pD2 values of 7.09 +/- 0.54, showing no difference from the untreated ones. On the other hand, preincubation with lipoxygenase inhibitors, nordihydroguaiaretic acid (NDGA) (3 X 10(-5)M) and AA861 (2 X 10(-5)M), prevented ACh-induced relaxation. The same trend was noted with the relaxation response induced by A23187. These results suggest that endothelium-derived relaxation of the canine uterine artery by ACh and A23187 may be mediated by a noncyclooxygenase metabolite(s). It was speculated that such inhibition of releasing EDRF has certain effects on the pathogenesis of toxemia and IUGR.