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

Chang-Lin Zhen1, Jie Yan1, Yu Zhao1

  • 1Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin 150086, PR China.

European Journal of Pharmacology
|February 7, 2016
PubMed
Summary

Taurochenodeoxycholate (TCDC) relaxes rat mesenteric arteries by activating endothelial nitric oxide synthase (eNOS). This bile acid conjugate shows potential for vasorelaxation in vivo, particularly in liver disease contexts.

Keywords:
GlycochenodeoxycholateTaurochenodeoxycholateTauroursodeoxycholateVasorelaxationeNOS

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Area of Science:

  • Cardiovascular Physiology
  • Hepatology
  • Endocrinology

Background:

  • Bile acids (BAs) and their conjugates possess vascular activities.
  • Elevated serum levels of BAs and conjugates are observed in liver diseases.
  • Understanding the vasoactivity of specific BA conjugates is crucial for disease management.

Purpose of the Study:

  • To investigate the in vitro vasoactivities of taurochenodeoxycholate (TCDC), glycochenodeoxycholate (GCDC), and tauroursodeoxycholate (TUDC).
  • To determine the mechanisms underlying the vasoactive effects of these bile acid conjugates.
  • To assess the potential role of TCDC in vasorelaxation in rat mesenteric arteries and thoracic aorta.

Main Methods:

  • Isometric tension recordings using multi-wire myograph systems in rat mesenteric arteries and thoracic aorta.
  • Assessment of relaxation responses to phenylephrine (PE) and high potassium (K+) induced contractions.
  • Evaluation of the effects of L-NAME and measurement of phosphorylated endothelial nitric oxide synthase (P-eNOS) expression.

Main Results:

  • Taurochenodeoxycholate (TCDC) induced concentration-dependent relaxation in endothelium-intact mesenteric arteries, an effect inhibited by L-NAME and linked to increased P-eNOS.
  • Glycochenodeoxycholate (GCDC) showed dose-dependent relaxation in both intact and denuded mesenteric arteries against PE, but not high K+.
  • TUDC and GCDC/TCDC in thoracic aorta exhibited no significant vasorelaxant effects.

Conclusions:

  • Taurochenodeoxycholate (TCDC) relaxes rat mesenteric arteries via endothelial nitric oxide synthase (eNOS) activation.
  • TCDC is identified as a significant bile acid conjugate potentially responsible for vasorelaxation in vivo.
  • These findings highlight the vascular implications of bile acid dysregulation in liver conditions.