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

Mark C. Lanasa, W. Allen Hogge, Carolyn J. Kubik, Roberta B. Ness, James Harger, Theodore Nagel, Tracy Prosen, Nina Markovic, Eric P. Hoffman

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

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
Volume185
Issue number3
DOIs
StatePublished - 2001

Keywords

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

PubMed: MeSH publication types

  • Journal Article

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