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.
© 2014 S. Karger AG, Basel.