Figure 9.

The underlying mechanisms of the SOCE/EDH-mediated vasorelaxation of mesenteric arteries in health and its impairments in the pathogenesis of colitis. The SOCE/EDH-mediated vasorelaxation in health (left panel) and its impairments in colitis (right panel). CPA inhibits the SERCA to activate the SOCE and induce Ca²⁺ signaling that stimulates IK_Ca and SK_Ca on vascular endothelial cells (VEC), leading to K⁺ efflux. An increase in extracellular K⁺ between VEC and VSMC activates NKA to eventually cause vasorelaxation through hyperpolarization. Moreover, NKA activation reduces [Na⁺]_i in VSMC, which stimulates Na⁺/Ca²⁺-exchange (NCX) activity to decreases [Ca²⁺]_i, resulting in further vasorelaxation. However, the SOCE/EDH-mediated vasorelaxation is likely impaired by inflammatory factors-induced endothelial dysfunction in the pathogenesis of colitis. SOCE, store operated Ca²⁺ entry; VEC, vascular endothelial cells; VSMC, vascular smooth muscle cells; SERCA, sarcoendoplasmic reticulum calcium transport ATPase, IK_Ca and SK_Ca: intermediate and small conductance of Ca²⁺-activated K⁺ channels; NKA, Na⁺/K⁺-ATPase; and NCX, Na⁺/Ca²⁺-exchanger.