TRPC3 is involved in flow- and bradykinin-induced vasodilation in rat small mesenteric arteries1

Abstract

To test the possible involvement of TRPC3 in agonist-induced relaxation and flow-induced vasodilation in rat small mesenteric arteries. Male Sprague-Dawley rats were used in the present study. After 72 h-treatment of antisense oligo via tail vein injection, isometric tension and isobaric diameter measurement were carried out with isolated mesenteric artery segments by using either a Pressure Myograph or a Multi Myograph system. Endothelial [Ca(2+)]i changes were measured with a MetaFluor imaging system in response to flow or to 30 nmol/L bradykinin. Immunohistochemical study showed that the 72 h-treatment of antisense oligo via tail vein injection markedly decreased the TRPC3 expression in mesenteric arteries, indicating the effectiveness of the antisense oligo. Isometric tension and isobaric diameter measurement showed that, although the antisense oligo treatment did not affect histamine-, ATP-, and CPA-induced relaxation, it did reduce the magnitude of flow-induced vasodilation by approximately 13% and decreased bradykinin-induced vascular relaxation with its EC50 value raised by nearly 3-fold. Endothelial [Ca(2+)]i measurement revealed that treatment of the arteries with antisense oligos significantly attenuated the magnitude of endothelial [Ca(2+)]i rise in response to flow and to 30 nmol/L bradykinin. The results suggest that TRPC3 is involved in flow- and bradykinin-induced vasodilation in rat small mesenteric arteries probably by mediating the Ca(2+) influx into endothelial cells.