Thyroxine Induces Acute Relaxation of Rat Skeletal Muscle Arteries via Integrin αvβ3, ERK1/2 and Integrin-Linked Kinase

Ekaterina K Selivanova; Dina K Gaynullina; Olga S Tarasova

doi:10.3389/fphys.2021.726354

Thyroxine Induces Acute Relaxation of Rat Skeletal Muscle Arteries via Integrin αvβ3, ERK1/2 and Integrin-Linked Kinase

Front Physiol. 2021 Sep 14:12:726354. doi: 10.3389/fphys.2021.726354. eCollection 2021.

Authors

Ekaterina K Selivanova¹, Dina K Gaynullina^{1

2}, Olga S Tarasova^{1

3}

Affiliations

¹ Department of Human and Animal Physiology, Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, Russia.
² Department of Physiology, Pirogov Russian National Research Medical University, Moscow, Russia.
³ Laboratory of Exercise Physiology, Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia.

Abstract

Aim: 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. Methods: Sural arteries from male Wistar rats were used for isometric force recording (wire myography) and phosphorylated protein content measurement (Western blotting). Results: Both triiodothyronine (T3) and thyroxine (T4) reduced contractile response of sural arteries to α₁-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). Conclusion: 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 α₁-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.

Keywords: integrin αvβ3; integrin-linked kinase; non-genomic effect; smooth muscle; sural artery; thyroxine.