Maximal radial artery flow-mediated dilatation was decreased by l-NMMA (-39%), tetraethylammonium chloride (-14%), fluconazole (-18%), and their combinations (up to -71%) compared to saline.
Does the inhibition of NO synthase, calcium-activated potassium channels, and cytochrome epoxygenases reduce sustained conduit artery flow-mediated dilatation in healthy subjects?
This study demonstrates that both NO and a cytochrome-related EDHF are involved in peripheral conduit artery flow-mediated dilatation in humans during sustained flow conditions, with synergistic effects suggesting functional interaction.
Whether NO is involved or not in sustained conduit artery flow-mediated dilatation in humans remains unclear. Moreover, the role of endothelium-derived hyperpolarizing factor (EDHF), synthesized by cytochrome epoxygenases and acting through calcium-activated potassium channels, and its relationship with NO during flow-mediated dilatation have never been investigated previously. In 12 healthy subjects we measured radial artery diameter (echotracking) and blood flow (Doppler) during flow-mediated dilatation induced by gradual distal hand skin heating (34 to 44 degrees C), during the local infusion of saline and inhibitors of NO synthase (N(G)-monomethyl-l-arginine l-NMMA: 8 to 20 micromol/min per liter), calcium-activated potassium channels (tetraethylammonium chloride: 9 micromol/min per liter), and cytochrome epoxygenases (fluconazole: 0.4 to 1.6 micromol/min per liter), alone and in combination. Mean wall shear stress, the flow-mediated dilatation stimulus, was calculated at each level of flow, and the diameter-wall shear stress relationship was constructed. During heating, compared with saline, the diameter-shear stress relationship was shifted downward by l-NMMA, tetraethylammonium, fluconazole, and, in a more pronounced manner, by the combinations of l-NMMA with tetraethylammonium or with fluconazole. Therefore, maximal radial artery flow-mediated dilatation, compared with saline (0.62+/-0.03 mm), was decreased under our experimental conditions by l-NMMA (-39+/-4%), tetraethylammonium chloride (-14+/-4%), fluconazole (-18+/-6%), and to a greater extent, by the combinations of l-NMMA with tetraethylammonium (-64+/-4%) or with fluconazole (-71+/-3%). This study demonstrates that NO and a cytochrome-related EDHF are involved in peripheral conduit artery flow-mediated dilatation in humans during sustained flow conditions. Moreover, the synergistic effects of the inhibitors strongly suggest a functional interaction between NO and EDHF pathways.
Bellien et al. (Tue,) conducted a other in Healthy (n=12). Inhibitors of NO synthase, calcium-activated potassium channels, and cytochrome epoxygenases vs. Saline was evaluated on Maximal radial artery flow-mediated dilatation. Maximal radial artery flow-mediated dilatation was decreased by l-NMMA (-39%), tetraethylammonium chloride (-14%), fluconazole (-18%), and their combinations (up to -71%) compared to saline.
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