Crucial Role of NO and Endothelium-Derived Hyperpolarizing Factor in Human Sustained Conduit Artery Flow-Mediated Dilatation

Hypertension - Tập 48 Số 6 - Trang 1088-1094 - 2006
Jérémy Bellien1, Michèle Iacob1, Laurence Gutierrez1, Marc Isabelle1, Agnès Lahary1, Christian Thuillez1, Robinson Joannidès1
1From the Departments of Pharmacology (J.B., M. Iacob, M. Isabelle, C.T., R.J.) and Hematology (A.L.) and Centre d’Investigation Clinique (L.G.), Institut National de la Santé et de la Recherche Médicale U644, Institut Fédératif de Recherche Multidisciplinaire sur les Peptides 23, Centre Hospitalier Universitaire-Hopitaux de Rouen, Rouen, France.

Tóm tắt

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°C), during the local infusion of saline and inhibitors of NO synthase ( N G -monomethyl- l -arginine [ l -NMMA]: 8 to 20 μmol/min per liter), calcium-activated potassium channels (tetraethylammonium chloride: 9 μmol/min per liter), and cytochrome epoxygenases (fluconazole: 0.4 to 1.6 μmol/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.

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Hypertension

Tập 48 Số 6

1088-1094

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