Pappas M, Mourouzis K, Karageorgiou H, Tesseromatis C, Mourouzis I, Kostopanagiotou G, Pantos C, Cokkinos D V
Department of Pharmacology, University of Athens, Athens, Greece.
Int Angiol. 2009 Dec;28(6):474-8.
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.
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).
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.
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.
甲状腺激素增加心输出量和降低全身血管阻力的能力可能为心血管疾病提供一种新的治疗方法。因此，了解甲状腺激素对心脏和外周血管系统的作用机制可能具有临床重要性。我们之前发现甲状腺激素可调节α1 - 肾上腺素能对大鼠主动脉血管反应性的影响。在本研究中，我们进一步探讨了这种反应的可能机制。
用左旋甲状腺素（L - 甲状腺素）对Wistar - Kyoto雄性大鼠进行为期两周的治疗以诱导甲状腺功能亢进，N = 18，未治疗的大鼠作为对照（正常组），N = 16。解剖胸主动脉并切成环，将其悬挂在含有克雷布斯 - 亨塞尔特缓冲液的离体器官浴中。在存在β2激动剂利托君的情况下（正常 - 利托君组，N = 8，甲状腺功能亢进 - 利托君组，N = 9），或在不存在利托君的情况下（甲状腺功能亢进组，N = 9，正常组，N = 8），测量环对氯化钾（KCl）和去氧肾上腺素（PE）的最大张力Tmax（以克为单位）。
使用KCl时，甲状腺功能亢进组、正常组、正常 - 利托君组和甲状腺功能亢进 - 利托君组之间的Tmax没有差异。使用PE时，正常 - 利托君组与正常组之间的Tmax存在差异，分别为0.66（0.056）克对1.00（0.066）克，P < 0.05；甲状腺功能亢进组与正常组之间也存在差异，分别为0.75（0.055）克对1.00（0.066）克，P < 0.05。甲状腺功能亢进 - 利托君组与甲状腺功能亢进组之间未观察到显著差异。此外，正常组与甲状腺功能亢进组、正常 - 利托君组和甲状腺功能亢进 - 利托君组之间的舒张百分比没有显著差异，分别为64.5%（3.7）对67.3%（6.7）、73.5%（4.3）和81.8%（4.7），P > 0.05。
利托君和甲状腺素治疗后，PE诱导的离体大鼠主动脉环血管收缩均减弱。然而，甲状腺激素与利托君联合使用并未导致PE诱导的血管收缩协同减弱。因此，甲状腺素可能通过增强β2 - 肾上腺素能刺激来调节α1 - 肾上腺素能血管反应性。
