The role of endothelium-derived hyperpolarizing factor in the regulation of the uterine circulation in pregnant rats

OBJECTIVE: The purpose of this study was to determine whether endothelium-d erived hyperpolarizing factor regulates rat uterine circulation in pregnant rats. STUDY DESIGN: Intact isolated uterine vascular beds from late pregnant rats were perfused in situ with Krebs buffer that contained dextran, indomethac in, N-nitro-L-arginine methyl ester, and phenylephrine. Endothelium-derived hyperpolarizing factor-induced decreases in perfusion pressure in response to acetylcholine were analyzed. RESULTS: The decrease in perfusion pressure induced by endothelium-derived hyperpolarizing factor was significantly attenuated by 4-aminopyridine and was abolished by a combination of 4-aminopyridine and tetraethylammonium. E ndothelium-derived hyperpolarizing factor-induced decrease in perfusion pre ssure was abolished by potassium chloride and attenuated by miconazole, but not linoleyl hydroxamic acid. Endothelium-derived hyperpolarizing factor-i nduced decrease in perfusion pressure persisted after perfusion with soluti ons that contained 2 inhibitors of nitric oxide synthase and a scavenger of nitric oxide. Nitric oxide exerted negative feedback on the endothelium-de rived hyperpolarizing factor effects. CONCLUSION; In the pregnant rat uterine vascular beds, endothelium-derived hyperpolarizing factor release is activated by a delayed rectifier type of voltage-sensitive potassium channel. Endothelium-derived hyperpolarizing fa ctor does not seem to be related to nitric oxide or to products of lipoxyge nase or cytochrome p450 mono-oxygenase pathways of arachidonic acid metabol ism.