title: The Nebivolol action on vascular tone is dependent on actin cytoskeleton polymerization and Rho-A activity into ECs and SMCs.
abstract: 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.
authors.affiliation: Faculté de Médecine, Université de Lorraine, Vandoeuvre, lès-Nancy, France CNRS UMR 7561- Groupe de Mécanique et Ingénierie Cellulaire et Tissulaire, Vandoeuvre, lès-Nancy, France.
authors.forename: A
authors.initials: A
authors.lastname: Kadi
authors.affiliation: Faculté de Médecine, Université de Lorraine, Vandoeuvre, lès-Nancy, France CNRS UMR 7561- Groupe de Mécanique et Ingénierie Cellulaire et Tissulaire, Vandoeuvre, lès-Nancy, France.
authors.forename: N
authors.initials: N
authors.lastname: de Isla
authors.affiliation: Faculté de Médecine, Université de Lorraine, Vandoeuvre, lès-Nancy, France CNRS UMR 7561- Groupe de Mécanique et Ingénierie Cellulaire et Tissulaire, Vandoeuvre, lès-Nancy, France.
authors.forename: V
authors.initials: V
authors.lastname: Moby
authors.affiliation: Faculté de Médecine, Université de Lorraine, Vandoeuvre, lès-Nancy, France INSERM UMR 961-Laboratoire de Pharmacologie Cardiovasculaire, Vandoeuvre, lès-Nancy, France.
authors.forename: P
authors.initials: P
authors.lastname: Lacolley
authors.affiliation: Faculté de Médecine, Université de Lorraine, Vandoeuvre, lès-Nancy, France CNRS UMR 7561- Groupe de Mécanique et Ingénierie Cellulaire et Tissulaire, Vandoeuvre, lès-Nancy, France.
authors.forename: P
authors.initials: P
authors.lastname: Labrude
authors.affiliation: Faculté de Médecine, Université de Lorraine, Vandoeuvre, lès-Nancy, France CNRS UMR 7561- Groupe de Mécanique et Ingénierie Cellulaire et Tissulaire, Vandoeuvre, lès-Nancy, France CHU -Cell and Tissue Therapy Unit, Vandoeuvre les Nancy, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Stoltz
authors.affiliation: Faculté de Médecine, Université de Lorraine, Vandoeuvre, lès-Nancy, France CNRS UMR 7561- Groupe de Mécanique et Ingénierie Cellulaire et Tissulaire, Vandoeuvre, lès-Nancy, France.
authors.forename: P
authors.initials: P
authors.lastname: Menu
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D001578:Benzopyrans / Q000378:metabolism*; D042783:Endothelial Cells; D004983:Ethanolamines / Q000378:metabolism*; D006801:Humans; D000068577:Nebivolol; D009569:Nitric Oxide / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism*; D058105:Polymerization; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D054460:rho-Associated Kinases
keywords: Nebivolol; Rho-kinase; actin cytoskeleton; eNOS; endothelial cell; nitric oxide; β blocker