Effective contractile response to voltage-gated Na+ channels revealed by a channel activator

This study investigated the molecular identity and impact of enhancing voltage-gated Na+ (NaV) channels in the control of vascular tone. In rat isolated mesenteric and femoral arteries mounted for isometric tension recording, the vascular actions of the NaV channel activator veratridine were examined. NaV channel expression was probed by molecular techniques and immunocytochemistry. In mesenteric arteries, veratridine induced potent contractions (pEC50 = 5.19 ± 0.20, Emax = 12.0 ± 2.7 mN), which were inhibited by 1 μM TTX (a blocker of all NaV channel isoforms, except NaV1.5, NaV1.8, and NaV1.9), but not by selective blockers of NaV1.7 (ProTx-II, 10 nM) or NaV1.8 (A-80347, 1 μM) channels. The responses were insensitive to endothelium removal but were partly (∼60%) reduced by chemical destruction of sympathetic nerves by 6-hydroxydopamine (2 mM) or antagonism at the α1-adrenoceptor by prazosin (1 μM). KB-R7943, a blocker of the reverse mode of the Na+/Ca2+ exchanger (3 μM), inhibited veratridine contractio...