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

Eva E. Fulep, Yuri P. Vedernikov, George R. Saade, Robert E. Garfield

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


OBJECTIVE: The purpose of this study was to determine whether endothelium-derived 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, indomethacin, 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. Endothelium-derived hyperpolarizing factor-induced decrease in perfusion pressure was abolished by potassium chloride and attenuated by miconazole, but not linoleyl hydroxamic acid. Endothelium-derived hyperpolarizing factor - Induced decrease in perfusion pressure persisted after perfusion with solutions that contained 2 inhibitors of nitric oxide synthase and a scavenger of nitric oxide. Nitric oxide exerted negative feedback on the endothelium-derived 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 factor does not seem to be related to nitric oxide or to products of lipoxygenase or cytochrome p450 mono-oxygenase pathways of arachidonic acid metabolism.

Original languageEnglish (US)
Pages (from-to)638-642
Number of pages5
JournalAmerican journal of obstetrics and gynecology
Issue number3
StatePublished - 2001


  • Endothelium
  • Endothelium-derived hyperpolarizing factor (EDHF)
  • Nitric oxide (NO)
  • Smooth muscle
  • Uterine vascular bed

ASJC Scopus subject areas

  • Obstetrics and Gynecology


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