Role of endothelium-derived hyperpolarizing factor in the regulation of radial artery basal diameter and endothelium-dependent dilatation in vivo.
1. The role of the balance between nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), synthesized by cytochrome epoxygenase and acting through calcium-activated potassium channels, in the regulation of basal diameter and endothelium-dependent flow-mediated dilatation of conduit arteries has been poorly assessed in humans. 2. Radial artery diameter and flow (echotracking coupled to Doppler) were measured in healthy volunteers under basal conditions and during flow-mediated dilatation induced by hand skin heating, in the presence of saline and inhibitors of NO-synthase, N(G)-monomethyl-L-arginine (L-NMMA), calcium-activated potassium channels, tetraethylammonium (TEA) and cytochrome epoxygenases, fluconazole, infused alone and in combination. Mean wall shear stress, the flow-mediated dilatation stimulus, was calculated and taken as cofactor into statistical analysis. 3. Under basal conditions, the radial artery diameter was not affected by L-NMMA and fluconazole infused alone but was decreased by TEA, the combinations of L-NMMA + fluconazole and, to a greater extent, L-NMMA + TEA. During heating, radial artery diameter increased with temperature in all cases. This increase in diameter, compared with saline, was reduced by L-NMMA, TEA, fluconazole and to a greater extent, by L-NMMA + TEA and L-NMMA + fluconazole. 4. These data show that EDHF is involved in balance with NO in the regulation of basal diameter and endothelium-dependent dilatation of human peripheral conduit arteries. The alteration of this balance could play a major role in the physiopathology of the endothelial dysfunction, in particular during essential hypertension.
Bellien
Jeremy
J
Department of Pharmacology, Rouen University Hospital and INSERM U644, IFRMP 23, Institute for Biomedical Research, University of Rouen, France.
Thuillez
Christian
C
Joannides
Robinson
R
D001685:Biological Factors / Q000378:metabolism*; D004727:Endothelium / Q000187:drug effects / Q000502:physiology*; D015725:Fluconazole / Q000494:pharmacology; D006358:Hot Temperature; D006801:Humans; D008297:Male; D017534:Radial Artery / Q000033:anatomy & histology* / Q000502:physiology*; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D019323:omega-N-Methylarginine; D019789:Tetraethylammonium; D015725:Fluconazole