We have demonstrated a functional role of voltage-gated sodium channels (Nav) in the regulation of blood contraction of rat aortas (Fort et al. 2009). These channels present in smooth muscle level in different human arterial beds (aorta, coronary artery, uterine, mammary) confer myocytes a track regulation of intracellular sodium ([Na +] i) (Quignard et al. Circ. Res., 1997 ;Boccara et al. Circ Res, 1999) and therefore calcium homeostasis via the exchanger Na + / Ca2 +.
The activity of Nav in human arteries appears to be related to the initiation and maintenance of rhythmical contractile oscillations known under the term of vasomotion and observed under hypoxic conditions. Ranolazine inhibitor persistent cardiac sodium current used in treating angina pectoris, vascular target Nav, presumably their inhibition contributes to the therapeutic benefit of the molecule (Virsolvy et al, submitted publication).
Our current efforts are focused on understanding the regulation (hypoxia, mechanosensitivity) and the pathophysiology of Nav, particularly hypertension and phenomena vasomotion. We also extend our investigations to human pulmonary arteries.
- PL Tharaux (PARCC, Paris), C.
- Oiry (IBMM, Montpellier)
Major Publications :
- Dechanet C, Fort A, Barbero-Camps E, Dechaud H, Richard S, Virsolvy A. Endothelin-dependent vasoconstriction in human uterine artery: application to preeclampsia. PLoS One, 2011, 6(1):e16540.
- Bardy G, Virsolvy A, Quignard JF, Ravier MA, Bertrand G, Dalle S, Cros G, Magous R, Richard S, Oiry C. Quercetininduces insulin secretion by direct activation of L-type calcium channels in pancreatic beta cells.. Br J Pharmacol. 2013 Jul;169(5):1102-13
- Lenoir O, Milon M, Virsolvy A, Hénique C, Schmitt A, Massé JM, Kotelevtsev Y, Yanagisawa M, Webb DJ, Richard S, Tharaux PL. Direct action of endothelin-1 on podocytes promotes diabetic glomerulosclerosis.. J Am Soc Nephrol. 2014 May;25(5):1050-62.