Vascular Function of the Mesenteric Artery Isolated from Thyroid Hormone Receptor-E Knockout Mice

Objective: This study evaluated the consequences of thyroid hormone receptor-E (TRE) disruption on vascular reactivity. Methods: The activity of superior mesenteric arteries isolated from TRE knockout mice generated in the SV129 background (TRE0/0SV) or in a pure C57BL/6 background (TRE0/0C57) 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 TRE 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 TRE0/0C57 mice. The administration of 3,3′5-triiodo-<smlcap>L</smlcap>-thyronine sodium salt (T₃) elicited a vasodilatation in C57BL/6 mice even at the lowest concentration (10⁻⁹<smlcap>M</smlcap>); a maximal relaxation of more than 50% was observed with the concentrations between 10⁻⁹ and 10⁻⁸<smlcap>M</smlcap>. However, the response to T₃ was nearly absent in TRE0/0C57 mice. Conclusion: TRE 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. i 2014 S.