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 (TRα0/0SV) or in a pure C57BL/6 background (TRα0/0C57) 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 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 TRα0/0C57 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 (10-9M); a maximal relaxation of more than 50% was observed with the concentrations between 10-9 and 10-8M. However, the response to T3 was nearly absent in TRα0/0C57 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.