Fiche publication
Date publication
janvier 2014
Journal
Clinical hemorheology and microcirculation
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MENU Patrick
,
Dr DE ISLA Natalia
Tous les auteurs :
Kadi A, de Isla N, Moby V, Lacolley P, Labrude P, Stoltz JF, Menu P
Lien Pubmed
Résumé
Nitric oxide is implicated in the target action of Nebivolol, a selective β1 adrenoceptor blocker used in hypertension treatment. As the Nitric Oxide (NO) production and the actin cytoskeleton are linked, the aim of this work was to study the involvement of actin cytoskeleton on mechanism of action of Nebivolol in cultured endothelial cells. We studied the effect of Nebivolol (200 μM) on actin filaments remodeling and its impact on NO production and eNOS activation. Results showed that Nebivolol perturbs actin filaments polymerization, increases NO production and eNOS activity between 30 minutes and 1 h. Stabilization of actin filaments with phalloïdine (50 μM) abolishes Nebivolol effects on eNOS activation and NO production. Furthermore, Rho-kinase activity decreased during the first hour of Nebivolol treatment, then increased after 3 h, while actin filaments repolymerized, eNOS activation and NO production decreased. In SMCs, Nebivolol induced a decrease in the Rho-kinase activity from 1 h until 24 h of incubation. In conclusion, we suggest that Nebivolol induced NO production in Endothelial Cells (ECs) via complementary actions between actin cytoskeleton remodeling inducing eNOS activation and Rho-kinase implication. The effect of Nebivolol on ECs occurs during the first hour, this effect on SMCs seems to be maintained until 24 h, explaining persisted action of Nebivolol observed in vivo.
Mots clés
Actin Cytoskeleton, metabolism, Benzopyrans, metabolism, Endothelial Cells, Ethanolamines, metabolism, Humans, Nebivolol, Nitric Oxide, pharmacology, Nitric Oxide Synthase Type III, genetics, Polymerization, rho-Associated Kinases, metabolism
Référence
Clin. Hemorheol. Microcirc.. 2014 ;56(3):231-46
