Endothelium-derived hyperpolarizing factor(s): Species and tissue heterogeneity

C. R. Triggle, H. Dong, G. J. Waldron, W. C. Cole

Research output: Contribution to journalArticle

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1. Endothelium-derivcd relaxing factor is almost universally considered to be synonymous with nitric oxide (NO); however, it is now well established that at least two other chemically distinct species (prostacyclin (PGI2) and a hyperpolarizing factor) may also contribute to endothelium-dependent relaxation. 2. Only relatively few studies have provided definitive evidence that an endothelium-derived hyperpolarizing factor (EDHF), which is neither NO nor PGI2, exists as a chemical mediator. 3. There is a lack of agreement as to the likely chemical identity of this putative factor. Some evidence suggests that EDHF may be a cytochrome P450-derived arachidonic acid product, possibly an epoxyeicosatrienoic acid (EET); conflict-ing evidence supports an endogenous cannabinoid as the mediator and still other studies infer an unknown mediator that is neither a cytochrome P450 nor a cannabinoid. 4. Data from our laboratory with a rabbit carotid artery 'sandwich' preparation have provided evidence that a mediator that meets the pharmacological expectations of a cytochrome P450 product is an EDHF. 5. Data from guinea-pig mesenteric arterioles suggest that EDHF is not a cytochrome P450 product, whereas in guinea-pig middle cerebral arteries, relaxation mediated by the NO/PGI2-independent mediator(s) is sensitive to cytochrome P450 inhibitors. In addition, in the rabbit middle cerebral artery, it is likely that endothelium-dependent hyperpolarization is mediated by both NO and PGI2. 6. In conclusion, these data indicate that EDHF is unlikely to be a single factor and that considerable tissue and species differences exist for the nature and cellular targets of the hyperpolarizing factors.

Original languageEnglish
Pages (from-to)176-179
Number of pages4
JournalClinical and Experimental Pharmacology and Physiology
Issue number2
Publication statusPublished - 1 Jan 1999



  • Cytochrome P
  • Endothelium
  • Endothelium-derived relaxing factor
  • Epoxyeicosatrienoic acid
  • Hyperpolarizing factor
  • K channels
  • Nitric oxide
  • Prostacyclin
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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