Taurochenodeoxycholate relaxes rat mesenteric arteries through activating eNOS: Comparing with glycochenodeoxycholate and tauroursodeoxycholate

摘要

The bile acids (BAs) and their conjugates have vascular activities and the serum levels of BAs and their conjugates are increased in liver diseases. In the present study, we examined the in vitro vasoactivities of BAs conjugates taurochenodeoxycholate (TCDC) (5-80 mu M), glycochenodeoxycholate (GCDC) (20-150 mu M) and tauroursodeoxycholate (TUDC) (20-150 mu M) in rat mesenteric arteries and thoracic aorta. The isometric tension of rat mesenteric arteries and thoracic aorta was recorded by using multi-wire myograph systems. TCDC induced significant concentration-dependent relaxation in endothelium-intact but not endothelium-denuded rat mesenteric arteries pre-contracted with phenylephrine (PE). TCDC also showed vasorelaxant effects on high K+ induced contraction in rat mesenteric arteries. L-NAME treatment inhibited TCDC-induced relaxation in mesenteric arteries pre-contracted with PE. Acute treatment with TCDC increased protein expression of P-eNOS (ser1177) in human umbilical vein endothelial cells. GCDC dose-dependently relaxed PE-induced vasoconstriction in both endotheium-intact and endothelium-denuded rat mesenteric arteries, but GCDC showed no effect on high K+-induced vasoconstriction. Both GCDC and TCDC showed no apparent relaxation on PE and high K+-induced vasoconstriction in rat thoracic aorta. TUDC showed no effect on PE and high K+-induced vasoconstriction in rat mesenteric arteries and thoracic aorta. The study demonstrates that TCDC relaxes rat mesenteric arteries through activating eNOS. TCDC might be the major BAs conjugate for vasorelaxation in vivo. (C) 2016 Elsevier B.V. All rights reserved.