Vascular function of the mesenteric artery isolated from thyroid hormone receptor-α knockout mice

J Vasc Res. 2014;51(5):350-9. doi: 10.1159/000368195. Epub 2014 Dec 5.

Abstract

Objective: This study evaluated the consequences of thyroid hormone receptor-α (TRα) disruption on vascular reactivity.

Methods: The activity of superior mesenteric arteries isolated from TRα knockout mice generated in the SV129 background (TRα(0/0)SV) or in a pure C57BL/6 background (TRα(0/0)C57) was compared to that of their corresponding wild-type strains (SV129 or C57BL/6 mice).

Results: The wild-type SV129 mice exhibited an impaired acetylcholine (Ach)-induced mesenteric artery relaxation compared to C57BL/6 mice, associated with greater responses to angiotensin II (AII) and phenylephrine (PE). The disruption of TRα decreased the vascular response to sodium nitroprusside and PE in both the SV129 and C57BL/6 genetic backgrounds. Responses to Ach and AII were also blunted, but only in TRα(0/0)C57 mice. The administration of 3,3'5-triiodo-L-thyronine sodium salt (T3) elicited a vasodilatation in C57BL/6 mice even at the lowest concentration (10(-9)M); a maximal relaxation of more than 50% was observed with the concentrations between 10(-9) and 10(-8)M. However, the response to T3 was nearly absent in TRα(0/0)C57 mice.

Conclusion: TRα is essential for the control of vascular tone, particularly in thyroid hormone-mediated relaxation. The difference in response to Ach observed between the two wild-type mice should be taken into account for interpreting the vascular responses of genetically engineered mice.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Genotype
  • Male
  • Mesenteric Artery, Superior / drug effects
  • Mesenteric Artery, Superior / metabolism*
  • Mesenteric Artery, Superior / physiopathology
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Species Specificity
  • Thyroid Hormone Receptors alpha / agonists
  • Thyroid Hormone Receptors alpha / deficiency*
  • Thyroid Hormone Receptors alpha / genetics
  • Triiodothyronine / pharmacology
  • Vasoconstriction
  • Vasoconstrictor Agents / pharmacology
  • Vasodilation* / drug effects
  • Vasodilator Agents / pharmacology

Substances

  • Thyroid Hormone Receptors alpha
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Triiodothyronine