Farnesoid X receptor activation regulates vascular tension of rat mesenteric resistance arteries

Abstract

The peripheral vascular resistance is a critical determinant of blood pressure. The farnesoid X receptor (FXR) in the vasculature have been shown to regulate vascular tension of large vessels. In present work, we investigated whether FXR activation regulates vascular tension of rat mesenteric resistance arteries (MRA). We detected the protein abundances of Ang II type 1/2 receptor (AT1R, AT2R) and bradykinin type 1/2 receptor (B1R, B2R) following FXR stimulation. The endothelial/inducible NO synthase (eNOS/iNOS)/NO and cyclooxygenase (COX)/ thromboxane A2 (TXA2), and the vascular tone were also investigated following FXR activation with presence or absence of AT2R-B2R blockade. We found that the FXR ligands GW4064 and INT-747 increased the protein abundance of AT2R and B1/B2R. AT2R blockade with PD123319 reversed the effects of FXR agonists on levels of B2R but not B1R in MRAECs. Moreover, GW4064 and INT-747 upregulated the expression of eNOS and enhanced NOS activity, enhanced vasodilation, attenuated vasoconstriction and myogenic tone respectively, which were partially reversed by AT2R -B2R blockade. However, there were no significant effects of FXR-AT2R-B2R activation on COX1/2-TXA2 in MRAECs. The present study suggested that FXR-AT2R -B2R pathway activation regulated vascular tension of rat MRA through eNOS-NO but not COX-TXA2 pathway in physiological conditions.