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Critical contribution of Na + -Ca 2+ exchanger to the Ca 2+ -mediated vasodilation activated in endothelial cells of resistance arteries

Na -Ca exchanger (NCX) contributes to control the intracellular free Ca concentration ([Ca ] ), but the functional activation of NCX reverse mode (NCXrm) in endothelial cells is controversial. We evaluated the participation of NCXrm-mediated Ca uptake in the endothelium-dependent vasodilation of rat...

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Published in:The FASEB journal 2018-04, Vol.32 (4), p.2137-2147
Main Authors: Lillo, Mauricio A, Gaete, Pablo S, Puebla, Mariela, Ardiles, Nicolás M, Poblete, Inés, Becerra, Alvaro, Simon, Felipe, Figueroa, Xavier F
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description Na -Ca exchanger (NCX) contributes to control the intracellular free Ca concentration ([Ca ] ), but the functional activation of NCX reverse mode (NCXrm) in endothelial cells is controversial. We evaluated the participation of NCXrm-mediated Ca uptake in the endothelium-dependent vasodilation of rat isolated mesenteric arterial beds. In phenylephrine-contracted mesenteries, the acetylcholine (ACh)-induced vasodilation was abolished by treatment with the NCXrm blockers SEA0400, KB-R7943, or SN-6. Consistent with that, the ACh-induced hyperpolarization observed in primary cultures of mesenteric endothelial cells and in smooth muscle of isolated mesenteric resistance arteries was attenuated by KB-R7943 and SEA0400, respectively. In addition, both blockers abolished the NO production activated by ACh in intact mesenteric arteries. In contrast, the inhibition of NCXrm did not affect the vasodilator responses induced by the Ca ionophore, ionomycin, and the NO donor, S-nitroso- N-acetylpenicillamine. Furthermore, SEA0400, KB-R7943, and a small interference RNA directed against NCX1 blunted the increase in [Ca ] induced by ACh or ATP in cultured endothelial cells. The analysis by proximity ligation assay showed that the NO-synthesizing enzyme, eNOS, and NCX1 were associated in endothelial cell caveolae of intact mesenteric resistance arteries. These results indicate that the activation of NCXrm has a central role in Ca -mediated vasodilation initiated by ACh in endothelial cells of resistance arteries.-Lillo, M. A., Gaete, P. S., Puebla, M., Ardiles, N. M., Poblete, I., Becerra, A., Simon, F., Figueroa, X. F. Critical contribution of Na -Ca exchanger to the Ca -mediated vasodilation activated in endothelial cells of resistance arteries.
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subjects Animals
Calcium - metabolism
Cells, Cultured
Endothelial Cells - metabolism
Endothelium, Vascular - cytology
Endothelium, Vascular - metabolism
Male
Mesenteric Arteries - cytology
Mesenteric Arteries - metabolism
Mesenteric Arteries - physiology
Muscle, Smooth, Vascular - cytology
Muscle, Smooth, Vascular - metabolism
Muscle, Smooth, Vascular - physiology
Myocytes, Smooth Muscle - metabolism
Nitric Oxide - metabolism
Nitric Oxide Synthase Type III - metabolism
Rats
Rats, Sprague-Dawley
Sodium-Calcium Exchanger - antagonists & inhibitors
Sodium-Calcium Exchanger - metabolism
Vasodilation
title Critical contribution of Na + -Ca 2+ exchanger to the Ca 2+ -mediated vasodilation activated in endothelial cells of resistance arteries
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