In arterial smooth muscle cells, Piezo1 channels participate in the regulation of vascular tone and remodeling in various diseases. They are non-selective cation channels, the activation of which can lead to depolarization of the smooth muscle cell membrane, the entry of Ca through voltage-gated channels and the development of contraction. This study tested the hypothesis that Piezo1 channels participate in the regulation of smooth muscle cell tone in small cerebral arteries and their functional contribution change in chronic stenosis of the carotid arteries. Rats obtained constrictor clips on both common carotid arteries (reduction in blood flow velocity by at least 70%). After 4 weeks, the middle cerebral artery (MCA) was isolated for wire myography (after removal of endothelium) and quantitative PCR. The basal tone of the MCA was lower in the Stenosis group than in the control, and contractile responses to thromboxane A receptor agonist U46619 were not changed. Incubation with Dooku1 (Piezo1 blocker, 30 μM) resulted in a decrease in basal tone and contractile responses to U46619 in the MCA of control rats, but had no such effect in the MCA of the Stenosis group. The mRNA content of Piezo1 and L-type voltage-gated Ca channels (Ca1.2) did not differ between the groups, whereas the mRNA content of T-type voltage-gated Ca channels (Ca3.1) was reduced in the MCA of the Stenosis group compared to the control one. Thus, Piezo1 channels have a pro-contractile effect in the smooth muscle cells of rat cerebral arteries, and we have shown for the first time that such an effect decreases in chronic stenosis of the carotid arteries. The decrease in the pro-contractile effect of Piezo1 in the MCA of the Stenosis rats may be associated with the changes in not the Piezo1 channels themselves, but in the subsequent stages of signal transduction to the contractile apparatus of smooth muscle cells.
D.K. Gaynullina (Wed,) studied this question.