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).