Fig. 7.

Role of TRP channels in the vascular system. A: TRP channels expressed in endothelial cells (ECs) and smooth muscle cells (SMCs) are involved in various functions of ECs and SMCs, including vasorelaxation, vasoconstriction, endothelial permeability, myogenic tone regulation, and SMC proliferation. B: schematic diagram illustrating endothelium-dependent vasorelaxation, and agonists as well as stretch/pressure-induced vasoconstriction. Activation of TRPV4 or other TRP channels in ECs by shear stress induces vasorelaxation through at least 2 pathways: 1) Ca²⁺ entry-mediated by TRPV4 activates SK_Ca and IK_Ca, leading to hyperpolarization of ECs and relaxation of SMCs through myoendothelial coupling (gap junctions); 2) Ca²⁺ influx via TRP channels in ECs enhances the synthesis and release of vasodilator factors such as nitric oxide (NO), which can inhibit voltage-gated Ca²⁺ channels (VGCC) and TRPC6 via cGMP-dependent pathway to induce relaxation. In SMCs, TRPV4 activation by EETs or other agonists triggers SR Ca²⁺ release and activation of BK_Ca, leading to hyperpolarization and vasorelaxation. Activation of TRPC channels such as TRPC6 or TRPC3 in SMCs via G_q-linked GPCRs stimulation by agonists (ANG II, ET-1, or PE) causes depolarization, and subsequent activation of VGCC leading to vasoconstriction. Moreover, stretch or pressure-induced activation of TRP channels, such as TRPM4 and TRPP2, can also depolarize SMCs, resulting in vasoconstriction.