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Etude de la régulation de la production de l'oxyde nitrique, dans les cellules endothéliales, en réponse à un ß bloquant de troisième génération à action antihypertensive : Implication des filaments d'actines du cytosquelette

Abstract : Hypertension is one of the most widespread diseases which is caused by a rigidity of the vascular wall. The arteries rigidity is controlled by several vasoconstrictor and vasodilator agents. Nitric oxide (NO) is a vasodilator agent, produced by the endothelial cell (EC) in response to biochemical (acetylcholine, insulin...) or mechanical (shearing) stimulations. Its main function is to induce smouth muscle cells (SMC) relaxation to adapt the blood vessel to the imposed forces. It has been shown in the literature, that NO is implicated in the target action of some drugs, as Nébivolol, which is directed against hypertension. We know according to the literature that NO production and the structure of the actin cytoskleton are linked and that Nébivolol induces NO production. The aim of this work was to study the implication of cytoskeleton actin filaments in the Nébivolol action in EC and to evaluate the eNOS involvement in the mechanism. We found that Nébivolol increased NO production via a depolymerization of actin filaments during the first hour of incubation. This depolymerization resulted in the peri-nuclear translocation and the phosphorylation of the eNOS by Akt. After the first hour of incubation with Nébivolol, actin monomers were repolymerized leading to the dephosphorylation of the eNOS and the reduction in the NO production. However, it seems that the stress fibers formation is not the only mechanism required for eNOS inhibition. In fact, we have shown that eNOS translocation in the peri-membranar area, inhibited the enzyme activity after actin filaments disruption.
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Assia Kadi. Etude de la régulation de la production de l'oxyde nitrique, dans les cellules endothéliales, en réponse à un ß bloquant de troisième génération à action antihypertensive : Implication des filaments d'actines du cytosquelette. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2008. Français. ⟨NNT : 2008NAN10113⟩. ⟨tel-01748483⟩

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