Activation of voltage-gated sodium channel triggers vasorelaxation of mice mesenteric arteries

Abstract

The resistance arteries, essential for the microcirculation, are able to rapidly change their diameters to control blood flow. These changes or vasomotricity depend on two opposite processes which are flow-mediated dilatation and myogenic tone. At cellular level, numerous ion channels, such as Ca2+ channels and K+ channels are involved in the control of vascular tone (VT). Voltage-gated Na+ channels (Nav) have also been reported in blood vessel, but their implication in VT remains puzzling. Figueroa and al. (2007) have demonstrated that Nav expressed in mouse cremaster arterioles are involved in endothelial function. The aim of our study is to identify the Nav subtypes expressed in resistance artery and to define their implication in VT by combining physiological and pharmacological approaches. We used mesenteric arteries (MA) from 5-month-old C57BL/6 J male and female mice to characterize Nav expression at transcriptional level by RT-qPCR and at protein level by histoimmunostaining. To investigate their place in VF, wire myography and arteriography were employed. Three transcripts encoding Nav1.2 (scn2a), Nav1.3 (scn3a) and Nav1.5 (scn5a) were identified in MA. The immunolabelling of the cardiac subtype, Nav1.5 confirmed its expression in MA. Interestingly, we showed that Nav activation with veratridine (VTD) induced the vasorelaxation of pre-stimulated MA with U46619. Since the VTD-evoked relaxation response is totally obviated in presence of NO synthase inhibitor, L-NNA, we suggest that the opening of Nav expressed in endothelial cells and subsequent Na+ entry induce the NO pathway activation. Our data highlight the contribution of Nav in VT. Further experiments will be necessary to define the role of each Nav subtype in VTD-induced vasorelaxant response and to characterize the cellular pathway by which the NO synthase is activated by Na+ entry.