Selivanova Ekaterina K, Gaynullina Dina K, Tarasova Olga S
Department of Human and Animal Physiology, Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, Russia.
Department of Physiology, Pirogov Russian National Research Medical University, Moscow, Russia.
Front Physiol. 2021 Sep 14;12:726354. doi: 10.3389/fphys.2021.726354. eCollection 2021.
Hyperthyroidism is associated with a decreased peripheral vascular resistance, which could be caused by the vasodilator genomic or non-genomic effects of thyroid hormones (TH). Non-genomic, or acute, effects develop within several minutes and involve a wide tissue-specific spectrum of molecular pathways poorly studied in vasculature. We aimed to investigate the mechanisms of acute effects of TH on rat skeletal muscle arteries. Sural arteries from male Wistar rats were used for isometric force recording (wire myography) and phosphorylated protein content measurement (Western blotting). Both triiodothyronine (T3) and thyroxine (T4) reduced contractile response of sural arteries to α-adrenoceptor agonist methoxamine. The effect of T4 was more prominent than T3 and not affected by iopanoic acid, an inhibitor of deiodinase 2. Endothelium denudation abolished the effect of T3, but not T4. Integrin αvβ3 inhibitor tetrac abolished the effect of T4 in endothelium-denuded arteries. T4 weakened methoxamine-induced elevation of phospho-MLC2 (Ser19) content in arterial samples. The effect of T4 in endothelium-denuded arteries was abolished by inhibiting ERK1/2 activation with U0126 as well as by ILK inhibitor Cpd22 but persisted in the presence of Src- or Rho-kinase inhibitors (PP2 and Y27632, respectively). Acute non-genomic relaxation of sural arteries induced by T3 is endothelium-dependent and that induced by T4 is endothelium-independent. The effect of T4 on α-adrenergic contraction is stronger compared to T3 and involves the suppression of extracellular matrix signaling via integrin αvβ3, ERK1/2 and ILK with subsequent decrease of MLC2 (Ser19) phosphorylation.
甲状腺功能亢进与外周血管阻力降低有关，这可能是由甲状腺激素（TH）的血管舒张基因组或非基因组效应引起的。非基因组或急性效应在几分钟内就会出现，涉及广泛的组织特异性分子途径，而这些途径在血管系统中研究较少。我们旨在研究TH对大鼠骨骼肌动脉的急性效应机制。使用雄性Wistar大鼠的腓肠动脉进行等长力记录（线肌电图）和磷酸化蛋白含量测量（蛋白质免疫印迹法）。三碘甲状腺原氨酸（T3）和甲状腺素（T4）均降低了腓肠动脉对α-肾上腺素能受体激动剂甲氧明的收缩反应。T4的作用比T3更显著，且不受脱碘酶2抑制剂碘番酸的影响。内皮剥脱消除了T3的作用，但未消除T4的作用。整合素αvβ3抑制剂替曲膦消除了T4在内皮剥脱动脉中的作用。T4减弱了甲氧明诱导的动脉样本中磷酸化肌球蛋白轻链2（Ser19）含量的升高。用U0126抑制ERK1/2激活以及用整合素连接激酶抑制剂Cpd22消除了T4在内皮剥脱动脉中的作用，但在存在Src激酶抑制剂（PP2）或Rho激酶抑制剂（Y27632）的情况下该作用仍然存在。T3诱导的腓肠动脉急性非基因组舒张是内皮依赖性的，而T4诱导的是内皮非依赖性的。与T3相比，T4对α-肾上腺素能收缩的作用更强，且涉及通过整合素αvβ3、ERK1/2和整合素连接激酶抑制细胞外基质信号传导，随后降低肌球蛋白轻链2（Ser19）的磷酸化水平。
