Functional heterogeneity of endothelium-dependent vasorelaxation in different order branches of mesenteric artery in female/male mice.

Although the mouse mesenteric artery is widely used as a model of resistance vessels, it is unknown which order branch is the best representative and if there is a heterogeneity of vascular activity in different orders. We systematically compared the vasorelaxation between the mouse mesenteric artery's first- and second-order branches. The first- and second-order branches of the mesenteric artery (lumen diameter of >300 μm and 179.9 ± 11.1 μm, respectively) were taken from the location close to their branching points in wide-type (WT) and TRPV4^-/- (KO) mice. Vasorelaxation of the mesenteric artery was measured using a Danish DMT520A microvascular system. Acetylcholine (ACh) induced much greater vasorelaxation via TRPV4 channels/endothelium-dependent hyperpolarization (EDH/H₂S) in the second-order branch. The store-operated Ca²⁺ entry (SOCE) mediated much greater vasorelaxation via EDH in the second-order branch than that via NO in the first-order branch. However, capsaicin-induced vasorelaxation was much greater via TRPV1/NO and TRPV1/CGRP in the first-order branch than TRPV4/EDH only in the second-order branch. Moreover, sex differences in ACh-induced vasorelaxation were obviously in the first-order branch but marginally in the second-order branch. Mechanistically, the myoendothelial gap junction (MEGJ) is involved in ACh-induced vasorelaxation in the second-order branch but not in the first-order branch. However, endothelial IK_Ca and SK_Ca functions and endothelium-independent vasorelaxation were similar for both first- and second-order branches. TRPV1/NO/CGRP mediates endothelium-dependent vasorelaxation in the first-order branch as the best representative of conduit vessels, but TRPV4/EDH/H₂S mediates endothelium-dependent vasorelaxation in the second-order branch as the best representative of resistance vessels in mice.