title: Endothelial dysfunction in a murine model of thyroid hormone resistance.
abstract: 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 (TRbeta PV) knockin mouse model targeting the PV mutation to the thyroid hormone receptor beta gene locus.
  
  
  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).
  
  
  CONCLUSIONS
  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 beta receptor require further elucidation.
authors.affiliation: Centre for Endocrine and Diabetes Sciences, Cardiff University, Wales, UK.
authors.forename: P J D
authors.initials: PJ
authors.lastname: Owen
authors.forename: H
authors.initials: H
authors.lastname: Ying
authors.forename: D
authors.initials: D
authors.lastname: Lang
authors.forename: D
authors.initials: D
authors.lastname: Tomlinson
authors.forename: M J
authors.initials: MJ
authors.lastname: Lewis
authors.forename: S Y
authors.initials: SY
authors.lastname: Cheng
authors.forename: J H
authors.initials: JH
authors.lastname: Lazarus
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000503:physiopathology; D001018:Aortic Diseases / Q000235:genetics* / Q000503:physiopathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D018382:Thyroid Hormone Resistance Syndrome / Q000235:genetics*