Involvement of Na(+)/Ca(2+) exchanger in endothelial NO production and endothelium-dependent relaxation |
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Authors: | Schneider Jean-Christophe El Kebir Driss Chéreau Christiane Mercier Jean-Christophe Dall'Ava-Santucci Josette Dinh-Xuan A Tuan |
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Institution: | Service de Physiologie-Explorations Fonctionnelles, Centre Hospitalier Universitaire Cochon, Assistance Publique, H?pitaux de Paris, Université Paris 5, 75014 Paris, France. |
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Abstract: | Endothelial nitric oxide (NO) synthase (eNOS) is controlled by Ca(2+)/calmodulin and caveolin-1 in caveolae. It has been recently suggested that Na(+)/Ca(2+) exchanger (NCX), also expressed in endothelial caveolae, is involved in eNOS activation. To investigate the role played by NCX in NO synthesis, we assessed the effects of Na(+) loading (induced by monensin) on rat aortic rings and cultured porcine aortic endothelial cells. Effect of monensin was evaluated by endothelium-dependent relaxation of rat aortic rings in response to acetylcholine and by real-time measurement of NO release from cultured endothelial cells stimulated by A-23187 and bradykinin. Na(+) loading shifted the acetylcholine concentration-response curve to the left. These effects were prevented by pretreatment with the NCX inhibitors benzamil and KB-R7943. Monensin potentiated Ca(2+)-dependent NO release in cultured cells, whereas benzamil and KB-R7943 totally blocked Na(+) loading-induced NO release. These findings confirm the key role of NCX in reverse mode on Ca(2+)-dependent NO production and endothelium-dependent relaxation. |
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