title: Thyroid hormone modulates the responsiveness of rat aorta to alpha1-adrenergic stimulation: an effect due to increased activation of beta2-adrenergic signaling.
abstract: OBJECTIVE
  The ability of the thyroid hormone to increase cardiac output and to lower systemic vascular resistance may provide a novel treatment for cardiovascular diseases. Therefore, understanding the mechanisms of thyroid hormone action on the heart and peripheral vasculature could be of clinical importance. We previously found that thyroid hormone modulates the alpha1-adrenergic effect on vascular reactivity of rat aortas. In the present study we further investigated possible mechanisms of this response.
  
  
  METHODS
  Hyperthyroidism was induced on Wistar-Kyoto male rats with L-Thyroxine, (THYR) treatment for two weeks, N.=18 while untreated rats used as controls (NORM), N.=16. The thoracic aorta was dissected and cut into rings that were suspended in an isolated organ bath with Krebs-Henseleit buffer. Maximal tension, Tmax, in g was measured in response to Potassium Chloride (KCl) and Phenylephrine (PE) in rings in the presence of Ritodrine, a beta-2 agonist (NORM-RITO, N:=8, THYR-RITO, N.=9), or in the absence of Ritodrine (THYR, N.=9, NORM, N.=8).
  
  
  RESULTS
  With KCL, Tmax was not different between the THYR, NORM, NORM-RITO, and THYR-RITO groups. With PE, there was a difference in Tmax between NORM-RITO and NORM, 0.66 (0.056) g vs 1.00 (0.066) g, P<0.05 and THYR and NORM, 0.75 (0.055) g vs 1.00 (0.066) g, P<0.05. No significant difference was observed between THYR-RITO AND THYR. Furthermore, Relax % was not significantly different between the NORM and the THYR, NORM-RITO, and THYR-RITO groups, 64.5%(3.7) vs 67.3%(6.7), 73.5% (4.3) and 81.8 %(4.7), P>0.05.
  
  
  CONCLUSIONS
  PE induced vasoconstriction in isolated rat aortic rings was reduced after both ritodrine and thyroxine treatment. However, co-administration of thyroid hormone and ritodrine did not result in a synergistic reduction of PE induced vasoconstriction. Thus, thyroxine may modulate the alpha1-adrenergic vascular responsiveness by enhancing beta2-adrenergic stimulation.
authors.affiliation: Department of Pharmacology, University of Athens, Athens, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Pappas
authors.forename: K
authors.initials: K
authors.lastname: Mourouzis
authors.forename: H
authors.initials: H
authors.lastname: Karageorgiou
authors.forename: C
authors.initials: C
authors.lastname: Tesseromatis
authors.forename: I
authors.initials: I
authors.lastname: Mourouzis
authors.forename: G
authors.initials: G
authors.lastname: Kostopanagiotou
authors.forename: C
authors.initials: C
authors.lastname: Pantos
authors.forename: D V
authors.initials: DV
authors.lastname: Cokkinos
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006980:Hyperthyroidism / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D012312:Ritodrine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013974:Thyroxine / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D018340:Receptors, Adrenergic, alpha-1; D018343:Receptors, Adrenergic, beta-2; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D011189:Potassium Chloride; D012312:Ritodrine; D000109:Acetylcholine; D013974:Thyroxine