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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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
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| Series: | Toxins |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6651/16/12/533 |
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| Summary: | 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. |
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| ISSN: | 2072-6651 |