Novel endothelium-derived relaxing factors

Identification of factors and cellular targets

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22 Citations (Scopus)

Abstract

Nitric oxide (NO), together with prostacyclin (PGI2), mediates shear stress and endothelium-dependent vasodilator-mediated vasorelaxation. In the presence of inhibition of NO synthase (NOS) with nitroarginine analogues, such as of Nw-nitro-L-arginine methyl ester (L-NAME) and Nw-nitro-L-arginine (L-NNA), and indomethacin, to inhibit cyclooxygenase (COX) and the synthesis of PGI2, many blood vessels still respond with an endothelium-dependent relaxation to either chemical [i.e. acetylcholine (ACh)] or mechanical (shear stress) activation. This non-NO and non-PGI2 vasorelaxation appears to be mediated by hyperpolarization of the vascular smooth muscle cell (VSMC). Although NO can hyperpolarize VSMC, a novel mediator, the endothelium-derived hyperpolarizing factor (EDHF), which opens a VSMC K+ channel(s) notably in resistance vessels, has been proposed. Little agreement exists as to the nature of this putative factor, but several candidate molecules have been proposed and evidence, notably from the microcirculation, suggests that endothelium-dependent hyperpolarization (EDH) may be mediated via low electrical resistance coupling via myoendothelial gap junctions. We describe a number of techniques that are being used to identify EDHF and present data that address the contribution of a small increase in extracellular K+ as an EDHF.

Original languageEnglish
Pages (from-to)441-452
Number of pages12
JournalJournal of Pharmacological and Toxicological Methods
Volume44
Issue number2
DOIs
Publication statusPublished - Sep 2000
Externally publishedYes

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Endothelium-Dependent Relaxing Factors
Epoprostenol
Endothelium
Muscle
Vascular Smooth Muscle
Shear stress
Nitric Oxide
Smooth Muscle Myocytes
Microcirculation
Arginine
Acoustic impedance
Vasodilation
Nitroarginine
NG-Nitroarginine Methyl Ester
Blood vessels
Prostaglandin-Endoperoxide Synthases
Nitric Oxide Synthase
Indomethacin
Oxides
Acetylcholine

Keywords

  • Apamin
  • Charybdotoxin
  • Endothelium-derived hyperpolarizing factor
  • eNOS knockout mice
  • Extracellular K
  • K channels

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

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abstract = "Nitric oxide (NO), together with prostacyclin (PGI2), mediates shear stress and endothelium-dependent vasodilator-mediated vasorelaxation. In the presence of inhibition of NO synthase (NOS) with nitroarginine analogues, such as of Nw-nitro-L-arginine methyl ester (L-NAME) and Nw-nitro-L-arginine (L-NNA), and indomethacin, to inhibit cyclooxygenase (COX) and the synthesis of PGI2, many blood vessels still respond with an endothelium-dependent relaxation to either chemical [i.e. acetylcholine (ACh)] or mechanical (shear stress) activation. This non-NO and non-PGI2 vasorelaxation appears to be mediated by hyperpolarization of the vascular smooth muscle cell (VSMC). Although NO can hyperpolarize VSMC, a novel mediator, the endothelium-derived hyperpolarizing factor (EDHF), which opens a VSMC K+ channel(s) notably in resistance vessels, has been proposed. Little agreement exists as to the nature of this putative factor, but several candidate molecules have been proposed and evidence, notably from the microcirculation, suggests that endothelium-dependent hyperpolarization (EDH) may be mediated via low electrical resistance coupling via myoendothelial gap junctions. We describe a number of techniques that are being used to identify EDHF and present data that address the contribution of a small increase in extracellular K+ as an EDHF.",
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AU - Triggle, Christopher

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AB - Nitric oxide (NO), together with prostacyclin (PGI2), mediates shear stress and endothelium-dependent vasodilator-mediated vasorelaxation. In the presence of inhibition of NO synthase (NOS) with nitroarginine analogues, such as of Nw-nitro-L-arginine methyl ester (L-NAME) and Nw-nitro-L-arginine (L-NNA), and indomethacin, to inhibit cyclooxygenase (COX) and the synthesis of PGI2, many blood vessels still respond with an endothelium-dependent relaxation to either chemical [i.e. acetylcholine (ACh)] or mechanical (shear stress) activation. This non-NO and non-PGI2 vasorelaxation appears to be mediated by hyperpolarization of the vascular smooth muscle cell (VSMC). Although NO can hyperpolarize VSMC, a novel mediator, the endothelium-derived hyperpolarizing factor (EDHF), which opens a VSMC K+ channel(s) notably in resistance vessels, has been proposed. Little agreement exists as to the nature of this putative factor, but several candidate molecules have been proposed and evidence, notably from the microcirculation, suggests that endothelium-dependent hyperpolarization (EDH) may be mediated via low electrical resistance coupling via myoendothelial gap junctions. We describe a number of techniques that are being used to identify EDHF and present data that address the contribution of a small increase in extracellular K+ as an EDHF.

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