2018
DOI: 10.1096/fj.201700365rr
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Critical contribution of Na + ‐Ca 2+ exchanger to the Ca 2+ ‐mediated vasodilation activated in endothelial cells of resistance arteries

Abstract: 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 t… Show more

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Cited by 29 publications
(34 citation statements)
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“…However, there was no significant change in the initial Ca 2+ peak ( Figure 9F), in the plateau amplitude ( Figure 9F), or in the AUC ( Figure 9H). The same findings were obtained when the Ca 2+ signal induced by 300 µM ATP was measured in the presence of SEA0400 (SEA) (3 µM), which blocks both the forward and reverse mode of NCX [45] (Figure 10). Overall, these results demonstrate that NCX negatively regulates intracellular Ca 2+ clearing when rat aortic endothelium is stimulated with low (i.e., 20 µM) ATP concentration, although this effect significantly reduces the AUC only in LZDF rats.…”
Section: Ncx Activity Is Not Altered In Native Aortic Endothelium Of supporting
confidence: 75%
“…However, there was no significant change in the initial Ca 2+ peak ( Figure 9F), in the plateau amplitude ( Figure 9F), or in the AUC ( Figure 9H). The same findings were obtained when the Ca 2+ signal induced by 300 µM ATP was measured in the presence of SEA0400 (SEA) (3 µM), which blocks both the forward and reverse mode of NCX [45] (Figure 10). Overall, these results demonstrate that NCX negatively regulates intracellular Ca 2+ clearing when rat aortic endothelium is stimulated with low (i.e., 20 µM) ATP concentration, although this effect significantly reduces the AUC only in LZDF rats.…”
Section: Ncx Activity Is Not Altered In Native Aortic Endothelium Of supporting
confidence: 75%
“…Perfusion of the Isolated Mesenteric Arterial Bed. Rats were anesthetized with xylazine and ketamine (10 and 90 mg/kg, i.p., respectively), and the mesenteric arterial bed was isolated as described by Lillo et al [18]. Briefly, the superior mesenteric artery was cannulated and the mesentery was perfused at 2 mL/min with a warmed (37°C) Tyrode buffer solution (in mM: 118 NaCl, 5.4 KCl, 2.5 CaCl 2 , 1.2 KH 2 PO 4 , 1.2 MgSO 4 , 23.8 NaHCO 3 , and 11.1 glucose) that was bubbled with 95% O 2 -5% CO 2 to yield pH 7.35-7.45.…”
Section: Methodsmentioning
confidence: 99%
“…These findings demonstrate tight coupling between VSMC Na + and Ca 2+ homeostasis. Mechanisms linking these processes may involve NCX, an antiporter that can operate in forward or reverse mode, depending on the combined effects of Na + and Ca 2+ gradients 17,18 . Increased [Na + ]i activates the reverse mode of NCX, allowing Ca 2+ entry via the exchanger into the VSMCs 41,42 .…”
Section: Vascular Dysfunction In Lina3 Ht Mice Involves Trpm2 and Ncxmentioning
confidence: 99%
“…Of these the plasmalemmal NCX is particularly important because its activity may be bimodal. In the forward mode NCX activation promotes Na + influx and Ca 2+ extrusion, however positive membrane potential and increased intracellular Na + favor reverse mode NCX activation causing Ca 2+ influx and increased [Ca 2+ ]i 17,18 . Although reverse mode NCX has been demonstrated in endothelial cells 19 , there has been debate regarding the influence of NCX operating in reverse mode in VSMCs and its role in vascular function is unclear 20,21 .…”
Section: Introductionmentioning
confidence: 99%