Premium
ENDOTHELIUM‐DERIVED HYPERPOLARIZING FACTOR(S): SPECIES AND TISSUE HETEROGENEITY
Author(s) -
Triggle CR,
Waldron H Dong, Gj,
Cole WC
Publication year - 1999
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.1999.03007.x
Subject(s) - endothelium derived hyperpolarizing factor , endothelium , epoxygenase , mediator , cytochrome p450 , prostacyclin , nitric oxide , arachidonic acid , cytochrome , pharmacology , bradykinin , epoxyeicosatrienoic acid , biology , chemistry , biochemistry , medicine , endocrinology , enzyme , receptor , charybdotoxin
1. Endothelium‐derived 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 (PGI 2 ) 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 PGI 2 , 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 P 450 ‐derived arachidonic acid product, possibly an epoxyeicosatrienoic acid (EET); conflicting evidence supports an endogenous cannabinoid as the mediator and still other studies infer an unknown mediator that is neither a cytochrome P 450 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 P 450 product is an EDHF. 5. Data from guinea‐pig mesenteric arterioles suggest that EDHF is not a cytochrome P 450 product, whereas in guinea‐pig middle cerebral arteries, relaxation mediated by the NO/PGI 2 ‐independent mediator(s) is sensitive to cytochrome P 450 inhibitors. In addition, in the rabbit middle cerebral artery, it is likely that endothelium‐dependent hyperpolarization is mediated by both NO and PGI 2 . 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.