Involvement of Na(+)/Ca(2+) exchanger in endothelial NO production and endothelium-dependent relaxation.
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.
Service de Physiologie-Explorations Fonctionnelles, Centre Hospitalier Universitaire Cochon, Assistance Publique, Hôpitaux de Paris, Université Paris 5, 75014 Paris, France.
Jean-Christophe
JC
Schneider
Driss
D
El Kebir
Christiane
C
Chéreau
Jean-Christophe
JC
Mercier
Josette
J
Dall'Ava-Santucci
A Tuan
AT
Dinh-Xuan
D000109:Acetylcholine / Q000494:pharmacology; D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D008985:Monensin / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000502:physiology*; D013552:Swine; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D007476:Ionophores; D019831:Sodium-Calcium Exchanger; D014665:Vasodilator Agents; C013407:benzamil; D009569:Nitric Oxide; D000584:Amiloride; D008985:Monensin; D013890:Thiourea; D000109:Acetylcholine