FIGURE 8.

Potential signaling pathways involved in non-genomic relaxation of rat skeletal muscle artery in response to thyroxine. T4 induces endothelium-independent vasorelaxation due to suppression of extracellular matrix signaling, in detail: 1—contraction in response to α₁-adrenoceptor agonist methoxamine increases arterial wall tension; 2—the tension activates integrin αvβ3 and downstream procontractile ERK1/2 signaling pathway which includes ILK and its targets MLCP and MLC; 3—T4 interacts with integrin αvβ3 at the site overlaying the site recognizing the extracellular matrix and, thereby, weakens the integrin signaling and methoxamine-induced contraction. Key participants of T4-induced vasorelaxation discovered in our study are shown in red. Src-kinase, ROCK and Akt also may participate in integrin-dependent signaling, but our data do not support their role in T4-induced vasorelaxation in skeletal muscle arteries. Sharp arrows show activation and blunt arrows—inhibition of the targets. α₁R, α₁-adrenoceptor; CaM, calmodulin; ILK, integrin-linked kinase; MLC, myosin light chain 2; MLCK, myosin light chain kinase; MLCP, myosin light chain phosphatase; MYPT1, PP1 and M20 are subunits of MLCP; ROCK, Rho-kinase.