Veratridine Induces Vasorelaxation in Mouse Cecocolic Mesenteric Arteries
The vegetal alkaloid toxin veratridine (VTD) is a selective voltage-gated Na<sup>+</sup> (Na<sub>V</sub>) channel activator, widely used as a pharmacological tool in vascular physiology. We have previously shown that Na<sub>V</sub> channels, expressed in arteries,...
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2024-12-01
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| author | Joohee Park Christina Sahyoun Jacinthe Frangieh Léa Réthoré Coralyne Proux Linda Grimaud Emilie Vessières Jennifer Bourreau César Mattei Daniel Henrion Céline Marionneau Ziad Fajloun Claire Legendre Christian Legros |
| author_facet | Joohee Park Christina Sahyoun Jacinthe Frangieh Léa Réthoré Coralyne Proux Linda Grimaud Emilie Vessières Jennifer Bourreau César Mattei Daniel Henrion Céline Marionneau Ziad Fajloun Claire Legendre Christian Legros |
| author_sort | Joohee Park |
| collection | DOAJ |
| description | The vegetal alkaloid toxin veratridine (VTD) is a selective voltage-gated Na<sup>+</sup> (Na<sub>V</sub>) channel activator, widely used as a pharmacological tool in vascular physiology. We have previously shown that Na<sub>V</sub> channels, expressed in arteries, contribute to vascular tone in mouse mesenteric arteries (MAs). Here, we aimed to better characterize the mechanisms of action of VTD using mouse cecocolic arteries (CAs), a model of resistance artery. Using wire myography, we found that VTD induced vasorelaxation in mouse CAs. This VTD-induced relaxation was insensitive to prazosin, an α1-adrenergic receptor antagonist, but abolished by atropine, a muscarinic receptor antagonist. Indeed, VTD–vasorelaxant effect was totally inhibited by the Na<sub>V</sub> channel blocker tetrodotoxin (0.3 µM), the NO synthase inhibitor L-NNA (20 µM), and low extracellular Na<sup>+</sup> concentration (14.9 mM) and was partially blocked by the NCX1 antagonist SEA0400 (45.4% at 1 µM). Thus, we assumed that the VTD-induced vasorelaxation in CAs was due to acetylcholine release by parasympathetic neurons, which induced NO synthase activation mediated by the NCX1-Ca<sup>2+</sup> entry mode in endothelial cells (ECs). We demonstrated NCX1 expression in ECs by RT-qPCR and immunohisto- and western immunolabelling. VTD did not induce an increase in intracellular Ca<sup>2+</sup> ([Ca<sup>2+</sup>]i), while SEA0400 partially blocked acetylcholine-triggered [Ca<sup>2+</sup>]i elevations in Mile Sven 1 ECs. Altogether, these results illustrate that VTD activates Na<sub>V</sub> channels in parasympathetic neurons and then vasorelaxation in resistance arteries, which could explain arterial hypotension after VTD intoxication. |
| format | Article |
| id | doaj-art-c5d1f236b67a4782b4798e924b7d5fb1 |
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| publishDate | 2024-12-01 |
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| spelling | doaj-art-c5d1f236b67a4782b4798e924b7d5fb12025-08-20T02:43:50ZengMDPI AGToxins2072-66512024-12-01161253310.3390/toxins16120533Veratridine Induces Vasorelaxation in Mouse Cecocolic Mesenteric ArteriesJoohee Park0Christina Sahyoun1Jacinthe Frangieh2Léa Réthoré3Coralyne Proux4Linda Grimaud5Emilie Vessières6Jennifer Bourreau7César Mattei8Daniel Henrion9Céline Marionneau10Ziad Fajloun11Claire Legendre12Christian Legros13Univ. Angers, INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, 49000 Angers, FranceUniv. Angers, INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, 49000 Angers, FranceUniv. Angers, INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, 49000 Angers, FranceUniv. Angers, INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, 49000 Angers, FranceUniv. Angers, INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, 49000 Angers, FranceUniv. Angers, INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, 49000 Angers, FranceUniv. Angers, INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, 49000 Angers, FranceUniv. Angers, INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, 49000 Angers, FranceUniv. Angers, INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, 49000 Angers, FranceUniv. Angers, INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, 49000 Angers, FranceNantes Université, CNRS, INSERM, l’Institut du thorax, 44000 Nantes, FranceLaboratory of Applied Biotechnology (LBA3B), Department of Cell Culture, Azm Center for Research in Biotechnology and Its Applications, EDST, Lebanese University, Tripoli 1300, LebanonUniv. Angers, INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, 49000 Angers, FranceUniv. Angers, INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, 49000 Angers, FranceThe vegetal alkaloid toxin veratridine (VTD) is a selective voltage-gated Na<sup>+</sup> (Na<sub>V</sub>) channel activator, widely used as a pharmacological tool in vascular physiology. We have previously shown that Na<sub>V</sub> channels, expressed in arteries, contribute to vascular tone in mouse mesenteric arteries (MAs). Here, we aimed to better characterize the mechanisms of action of VTD using mouse cecocolic arteries (CAs), a model of resistance artery. Using wire myography, we found that VTD induced vasorelaxation in mouse CAs. This VTD-induced relaxation was insensitive to prazosin, an α1-adrenergic receptor antagonist, but abolished by atropine, a muscarinic receptor antagonist. Indeed, VTD–vasorelaxant effect was totally inhibited by the Na<sub>V</sub> channel blocker tetrodotoxin (0.3 µM), the NO synthase inhibitor L-NNA (20 µM), and low extracellular Na<sup>+</sup> concentration (14.9 mM) and was partially blocked by the NCX1 antagonist SEA0400 (45.4% at 1 µM). Thus, we assumed that the VTD-induced vasorelaxation in CAs was due to acetylcholine release by parasympathetic neurons, which induced NO synthase activation mediated by the NCX1-Ca<sup>2+</sup> entry mode in endothelial cells (ECs). We demonstrated NCX1 expression in ECs by RT-qPCR and immunohisto- and western immunolabelling. VTD did not induce an increase in intracellular Ca<sup>2+</sup> ([Ca<sup>2+</sup>]i), while SEA0400 partially blocked acetylcholine-triggered [Ca<sup>2+</sup>]i elevations in Mile Sven 1 ECs. Altogether, these results illustrate that VTD activates Na<sub>V</sub> channels in parasympathetic neurons and then vasorelaxation in resistance arteries, which could explain arterial hypotension after VTD intoxication.https://www.mdpi.com/2072-6651/16/12/533veratridinevoltage-gated Na<sup>+</sup> channelNa<sup>+</sup>/Ca<sup>2+</sup> exchanger (NCX)mouse mesenteric arteriesmyographymesenteric and endothelial cell lines |
| spellingShingle | Joohee Park Christina Sahyoun Jacinthe Frangieh Léa Réthoré Coralyne Proux Linda Grimaud Emilie Vessières Jennifer Bourreau César Mattei Daniel Henrion Céline Marionneau Ziad Fajloun Claire Legendre Christian Legros Veratridine Induces Vasorelaxation in Mouse Cecocolic Mesenteric Arteries Toxins veratridine voltage-gated Na<sup>+</sup> channel Na<sup>+</sup>/Ca<sup>2+</sup> exchanger (NCX) mouse mesenteric arteries myography mesenteric and endothelial cell lines |
| title | Veratridine Induces Vasorelaxation in Mouse Cecocolic Mesenteric Arteries |
| title_full | Veratridine Induces Vasorelaxation in Mouse Cecocolic Mesenteric Arteries |
| title_fullStr | Veratridine Induces Vasorelaxation in Mouse Cecocolic Mesenteric Arteries |
| title_full_unstemmed | Veratridine Induces Vasorelaxation in Mouse Cecocolic Mesenteric Arteries |
| title_short | Veratridine Induces Vasorelaxation in Mouse Cecocolic Mesenteric Arteries |
| title_sort | veratridine induces vasorelaxation in mouse cecocolic mesenteric arteries |
| topic | veratridine voltage-gated Na<sup>+</sup> channel Na<sup>+</sup>/Ca<sup>2+</sup> exchanger (NCX) mouse mesenteric arteries myography mesenteric and endothelial cell lines |
| url | https://www.mdpi.com/2072-6651/16/12/533 |
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