Involvement of Na<sup>+</sup>/Ca<sup>2+</sup>exchanger in endothelial NO production and endothelium-dependent relaxation

Schneider, Jean-Christophe; Kebir, Driss El; Chéreau, Christiane; Mercier, Jean-Christophe; Dall’Ava-Santucci, Josette; Dinh-Xuan, Anh Tuan

doi:10.1152/ajpheart.00789.2001

Cited by 46 publications

(47 citation statements)

References 39 publications

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“…We found that KB-R7943 at low concentrations (up to 10 M) did not change ATP-induced Ca 2ϩ transients in MAECs, which is consistent with the finding that KB-R7943 at 1 M did not inhibit EDR (25). In addition, we found that the subtype of NCX in MAECs is NCX1.…”

Section: Discussionsupporting

confidence: 90%

“…This mechanism may enable endothelial cells to release an appropriate amount of NO by regulating increases in [Ca 2ϩ ] i . On the other hand, as shown in this study, the reverse mode of NCX increases [Ca 2ϩ ] i and evokes EDR in Na ϩ -loaded conditions (6,25,28). In pathophysiological situations such as under oxidative stress, excessive Na ϩ entry via redox-activated cation channels has been observed (2,8).…”

Section: Discussionsupporting

confidence: 58%

“…On the other hand, we previously reported that Na ϩ -K ϩ pump activation inhibits Ca 2ϩ mobilization in endothelial cells and thereby endothelium-dependent relaxation (EDR) (26). NCX is thought to contribute to endothelium-dependent control of vascular contractility (6,25,28). These results support the involvement of the reverse mode of NCX in Ca 2ϩ mobilization in endothelial cells.…”

mentioning

confidence: 56%

“…These data suggest that the reverse mode of NCX does not contribute to EDR under physiological conditions, since KB-R7943 inhibits the reverse mode of NCX1 at low concentration (IC 50 ϭ 1.2-2.4 M) (13). The reverse mode of NCX may contribute EDR in pathophysiological conditions such as Na ϩ -loaded conditions or hyponatremia (Ͻ100 mM) (25). On the other hand, KB-R7943 inhibited EDR at a high concentration (Ͼ10 M).…”

Section: Discussionmentioning

confidence: 86%

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Na⁺-K⁺ pump activation inhibits endothelium-dependent relaxation by activating the forward mode of Na⁺/Ca²⁺ exchanger in mouse aorta

Kim¹,

Seol²,

Liang³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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pump activation inhibits endothelium-dependent relaxation by activating the forward mode of Na ϩ /Ca 2ϩ exchanger in mouse aorta. Am J Physiol Heart Circ Physiol 289: H2020-H2029, 2005. First published July 1, 2005; doi:10.1152/ajpheart.00908.2004.-The effect of Na ϩ -K ϩ pump activation on endothelium-dependent relaxation (EDR) and on intracellular Ca 2ϩ concentration ([Ca 2ϩ ]i) was examined in mouse aorta and mouse aortic endothelial cells (MAECs). The Na ϩ -K ϩ pump was activated by increasing extracellular K ϩ concentration ([K ϩ ]o) from 6 to 12 mM. In aortic rings, the Na ϩ ionophore monensin evoked EDR, and this EDR was inhibited by the Na ϩ /Ca 2ϩ exchanger (NCX; reverse mode) inhibitor KB-R7943. Monensininduced Na ϩ loading or extracellular Na ϩ depletion (Na ϩ replaced by Li ϩ ) increased [Ca 2ϩ ]i in MAECs, and this increase was inhibited by KB-R7943. Na ϩ -K ϩ pump activation inhibited EDR and [Ca 2ϩ ]i increase (K ϩ -induced inhibition of EDR and [Ca 2ϩ ]i increase). The Na ϩ -K ϩ pump inhibitor ouabain inhibited K ϩ -induced inhibition of EDR. Monensin (Ͼ0.1 M) and the NCX (forward and reverse mode) inhibitors 2Ј4Ј-dichlorobenzamil (Ͼ10 M) or Ni 2ϩ (Ͼ100 M) inhibited K ϩ -induced inhibition of EDR and [Ca 2ϩ ]i increase. KB-R7943 did not inhibit K ϩ -induced inhibition at up to 10 M but did at 30 M. In current-clamped MAECs, an increase in [K ϩ ]o from 6 to 12 mM depolarized the membrane potential, which was inhibited by ouabain, Ni 2ϩ , or KB-R7943. In aortic rings, the concentration of cGMP was significantly increased by acetylcholine and decreased on increasing [K ϩ ]o from 6 to 12 mM. This decrease in cGMP was significantly inhibited by pretreating with ouabain (100 M), Ni 2ϩ (300 M), or KB-R7943 (30 M). These results suggest that activation of the forward mode of NCX after Na ϩ -K ϩ pump activation inhibits Ca 2ϩ mobilization in endothelial cells, thereby modulating vasomotor tone. extracellular potassium; sodium-potassium pump; forward mode of sodium/calcium exchanger; endothelial cells; intracellular calcium THE NA ϩ -K ϩ PUMP and the Na ϩ /Ca 2ϩ exchanger (NCX) have an important role in modulating vascular contractility. Na ϩ -K ϩ pump activation relaxes vascular smooth muscle by hyperpolarizing the membrane potential (19, 24), and Na ϩ -K ϩ pump inhibition contracts vascular smooth muscle through activating the reverse mode of NCX by Na ϩ accumulation in the myoplasm (9, 18).In endothelial cells, the roles of the Na ϩ -K ϩ pump and NCX are unclear and contradictory. It was reported that Na ϩ -K ϩ pump inhibition affects the synthesis or release of endothelium-derived relaxing factor(s) rather than its effector pathway (29). On the other hand, we previously reported that Na ϩ -K ϩ pump activation inhibits Ca 2ϩ mobilization in endothelial cells and thereby endothelium-dependent relaxation (EDR) (26). NCX is thought to contribute to endothelium-dependent control of vascular contractility (6,25,28). These results support the involvement of the reverse mode of NCX in Ca 2ϩ mobilization in e...

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 58%

mentioning

confidence: 56%

Section: Discussionmentioning

confidence: 86%

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Na⁺-K⁺ pump activation inhibits endothelium-dependent relaxation by activating the forward mode of Na⁺/Ca²⁺ exchanger in mouse aorta

Kim¹,

Seol²,

Liang³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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“…These proteins are localised in the plasmalemmal caveolae in close proximity to eNOS and participate in the control of sub-plasmalemmal intracellular Ca 2+ , which is of particular importance for modulation of eNOS activity [34,35]. The high affinity/low capacity PMCA is the principal Ca 2+ removal system in vascular endothelium [36].…”

Section: Additive Effects Of D-glucose and Insulin On Nitric Oxide Fomentioning

confidence: 99%

Acute effects of glucose and insulin on vascular endothelium

et al. 2004

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Aims/hypothesis. Chronic exposure to high concentrations of glucose has consistently been demonstrated to impair endothelium-dependent, nitric oxide (NO)-mediated vasodilation. In contrast, several clinical investigations have reported that acute exposure to high glucose, alone or in combination with insulin, triggers vasodilation. The aim of this study was to examine whether elevated glucose itself stimulates endothelial NO formation or enhances insulin-mediated endothelial NO release. Methods. We measured NO release and vessel tone ex vivo in porcine coronary conduit arteries (PCAs). Intracellular Ca 2+ was monitored in porcine aortic endothelial cells (PAECs) by fura-2 fluorescence. Expression of the Na + /glucose cotransporter-1 (SGLT-1) was assayed in PAECs and PCA endothelium by RT-PCR. Results. Stimulation of PCAs with D-glucose, but not the osmotic control L-glucose, induced a transient increase in NO release (EC 50 ≈10 mmol/l), mediated by a rise in intracellular Ca 2+ levels due to an influx from the extracellular space. This effect was abolished by inhibitors of the plasmalemmal Na + /Ca 2+ exchanger (dichlorobenzamil) and the SGLT-1 (phlorizin), which was found to be expressed in aortic and coronary endothelium. Alone, D-glucose did not relax PCA, but did augment the effect of insulin on NO release and vasodilation. Conclusions/interpretation. An increased supply of extracellular D-glucose appears to enhance the activity of the endothelial isoform of nitric oxide synthase by increasing intracellular Na + concentrations via SGLT-1, which in turn stimulates an extracellular Ca 2+ influx through the Na + /Ca 2+ exchanger. This mechanism may be responsible for glucose-enhanced, insulin-dependent increases in tissue perfusion (including coronary blood-flow), thus accelerating glucose extraction from the blood circulation to limit the adverse vascular effects of prolonged hyperglycaemia.

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The Calcium Signaling Mechanisms in Arterial Smooth Muscle and Endothelial Cells

Ottolini

Sonkusare

2021

Comprehensive Physiology

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The contractile state of resistance arteries and arterioles is a crucial determinant of blood pressure and blood flow. Physiological regulation of arterial contractility requires constant communication between endothelial and smooth muscle cells. Various Ca 2+ signals and Ca 2+ -sensitive targets ensure dynamic control of intercellular communications in the vascular wall. The functional effect of a Ca 2+ signal on arterial contractility depends on the type of Ca 2+ -sensitive target engaged by that signal. Recent studies using advanced imaging methods have identified the spatiotemporal signatures of individual Ca 2+ signals that control arterial and arteriolar contractility. Broadly speaking, intracellular Ca 2+ is increased by ion channels and transporters on the plasma membrane and endoplasmic reticular membrane. Physiological roles for many vascular Ca 2+ signals have already been confirmed, while further investigation is needed for other Ca 2+ signals. This article focuses on endothelial and smooth muscle Ca 2+ signaling mechanisms in resistance arteries and arterioles. We discuss the Ca 2+ entry pathways at the plasma membrane, Ca 2+ release signals from the intracellular stores, the functional and physiological relevance of Ca 2+ signals, and their regulatory mechanisms. Finally, we describe the contribution of abnormal endothelial and smooth muscle Ca 2+ signals to the pathogenesis of vascular disorders.

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Involvement of Na⁺/Ca²⁺exchanger in endothelial NO production and endothelium-dependent relaxation

Cited by 46 publications

References 39 publications

Na⁺-K⁺ pump activation inhibits endothelium-dependent relaxation by activating the forward mode of Na⁺/Ca²⁺ exchanger in mouse aorta

Na⁺-K⁺ pump activation inhibits endothelium-dependent relaxation by activating the forward mode of Na⁺/Ca²⁺ exchanger in mouse aorta

Acute effects of glucose and insulin on vascular endothelium

The Calcium Signaling Mechanisms in Arterial Smooth Muscle and Endothelial Cells

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Involvement of Na+/Ca2+exchanger in endothelial NO production and endothelium-dependent relaxation

Cited by 46 publications

References 39 publications

Na+-K+ pump activation inhibits endothelium-dependent relaxation by activating the forward mode of Na+/Ca2+ exchanger in mouse aorta

Na+-K+ pump activation inhibits endothelium-dependent relaxation by activating the forward mode of Na+/Ca2+ exchanger in mouse aorta

Acute effects of glucose and insulin on vascular endothelium

The Calcium Signaling Mechanisms in Arterial Smooth Muscle and Endothelial Cells

Contact Info

Product

Resources

About

Involvement of Na⁺/Ca²⁺exchanger in endothelial NO production and endothelium-dependent relaxation

Na⁺-K⁺ pump activation inhibits endothelium-dependent relaxation by activating the forward mode of Na⁺/Ca²⁺ exchanger in mouse aorta

Na⁺-K⁺ pump activation inhibits endothelium-dependent relaxation by activating the forward mode of Na⁺/Ca²⁺ exchanger in mouse aorta