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Thyroxine direct vasodilating effect in skeletal muscle artery is mediated by integrin αvβ3тезисы доклада
- Авторы: Selivanova E., Gaynullina D., Tarasova O.S.
- Сборник: Europhysiology 2018
- Тезисы
- Год издания: 2018
- Место издания: London
- Первая страница: 476
- Последняя страница: 476
- Аннотация: The thyroid hormones, triiodothyronine (T3) and thyroxine (T4), play essential roles in the regulation of almost all organ systems including the cardiovascular system. Traditionally their action was associated with activation of thyroid hormone receptors which alter the transcription of target genes (so-called genomic action). However, in the past two decades, the rapid nongenomic effects of thyroid hormones were discovered. Several authors had observed the direct relaxant action of thyroid hormones on small resistance arteries but the underlying mechanisms, in particular, the receptors mediating the arterial response, were not established. In some tissues, the nongenomic action of thyroid hormones is initiated by integrin αvβ3. The aim of this study was to explore the role of integrin αvβ3 in vasodilation induced by thyroid hormones. All experiments were performed on adult Wistar rats (body weight 250-350 g). Animals were killed by decapitation under CO2 anaesthesia, then sural arteries (d=260-380 micron) with intact endothelium were isolated and studied in a wire myograph. Arterial responses were analyzed with 2-way ANOVA, the significance level was set below 0.05 and n was 5-12 for each experimental group. T4 (0.02 to 10 microM) induced concentration-dependent vasorelaxation of the methoxamine-preconstricted vessels, the difference from time-control appeared starting from the concentration of 2 microM. T3 applied in the same concentration range did not induce vasorelaxation. The effect of T4 was not associated with its partial conversion to the T3 since the incubation with the deiodinase 2 inhibitor (iopanoic acid, 100 microM) did not alter the relaxation. In addition, the incubation with T4 (3 microM) diminished the maximum force and induced the leftward shift of methoxamine concentration- response curve (0.01 to 100 microM). The contractile responses of arteries incubated with T4 in the presence of tetrac (3 microM), a competitive inhibitor of integrin αvβ3, were not different from the responses of arteries, incubated with tetrac alone. These results suggest that the vasodilatory effect of T4 was mediated by integrin αvβ3. To conclude, in skeletal muscle arteries T4 has direct nongenomic relaxant effect mediated by the integrin αvβ3. Such data are relevant for improvement of our knowledge on T4 effects in the cardiovascular system. Moreover, the direct effects of T4 on the vasculature should be taken into account in hormone replacement therapy. Thyroid hormones could also have beneficial effects in the perioperative period of cardiac surgery because of their vasodilatory action on coronary arteries. The research was supported by the Russian Science Foundation (Grant N 14-15-00704).
- Добавил в систему: Селиванова Екатерина Константиновна