endothelium-derived hyperpolarizing factor.endothelium-dependent hyperpolarization.Suppression of TRPC6 channel activity in VSMCs could be a new strategy for the improvement of post-ischaemic peripheral blood circulation. Furthermore, inhibition of TRPC6 channel activity by pyrazole-2 (Pyr2 BTP2 YM-58483) promoted post-ischaemic blood flow recovery in A polipoprotein E-knockout mice. Cilostazol, a clinically approved drug for peripheral arterial disease, facilitates blood flow recovery by inactivating TRPC6 via phosphorylation at Thr69 in VSMCs. Key ResultsĪlthough the post-ischaemic blood flow recovery is reportedly dependent on endothelium-dependent relaxing factors, systemic TRPC6 deletion significantly promoted blood flow recovery under the condition that nitric oxide or prostacyclin production were inhibited, accompanying capillary arterialization. Expression and phosphorylation levels of TRPC6 proteins were determined by western blotting and immunohistochemistry. The number and diameter of blood vessels were analysed by immunohistochemistry.
The recovery rate of peripheral blood flow was calculated by the ratio of ischaemic left leg to non-ischaemic right one. Mice were subjected to hindlimb ischaemia by ligating left femoral artery. We here investigated whether TRPC6 inhibition promotes post-ischaemic blood flow recovery through capillary arterialization in vivo. We previously demonstrated that the inhibition of transient receptor potential 6 subfamily C, member 6 (TRPC6) channels facilitate contractile differentiation of VSMCs under ischaemic stress. Capillary arterialization, characterized by the coverage of pre-existing or nascent capillary vessels with vascular smooth muscle cells (VSMCs), is critical for the development of collateral arterioles to improve post-ischaemic blood flow.
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