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Endothelial dysfunction in a murine model of thyroid hormone resistance
Author(s) -
Owen P. J. D.,
Ying H.,
Lang D.,
Tomlinson D.,
Lewis M. J.,
Cheng S. Y.,
Lazarus J. H.
Publication year - 2007
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2007.01799.x
Subject(s) - endocrinology , medicine , hormone , thyroid , sodium nitroprusside , snp , phenylephrine , thyroid function , thyroid hormone receptor , biology , genotype , single nucleotide polymorphism , gene , genetics , nitric oxide , blood pressure
Background The development of a knockin mouse model of resistance to thyroid hormone (RTH) has led to a greater understanding of both the molecular and clinical behaviour of this syndrome. We have investigated the vascular response in RTH using a specific (TRβ PV) knockin mouse model targeting the PV mutation to the thyroid hormone receptor β gene locus. Materials and methods Ring segments of the thoracic aorta were used to assess the response of homozygous, heterozygous and wild‐type controls to contractile agents, potassium chloride and phenylephrine. Each genotype after maximal contraction was exposed to increasing concentrations of relaxing agents, acetylcholine (ACh) and sodium nitroprusside (SNP). Results The response of these aortic ring segments to ACh and SNP demonstrates that endothelium‐dependent relaxation to ACh was significantly impaired in both heterozygous and homozygous mice compared to controls (69·8 ± 2·0%, 59·7 ± 1·4% and 75·0 ± 1·7%, respectively; P < 0·001). However, endothelium independent responses to SNP showed no difference between genotypes (114·4 ± 3·2%, 116·8 ± 2·6% and 106·9 ± 4·9%; P = NS). Conclusion These data suggest that endothelial function is impaired in the RTH mouse aorta. The respective roles of elevated thyroid stimulating hormone (TSH), elevated thyroid hormone concentrations and the mutated thyroid hormone β receptor require further elucidation.