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Nutrient‐induced hyperosmosis evokes vasorelaxation via TRPV1‐mediated endothelium‐dependent hyperpolarization in healthy and colitis mice 营养素诱导的高渗透通过TRPV1介导的内皮依赖性超极化在健康和结肠炎小鼠中引起血管舒张 10.1111/bph.15322 11-09, Article Abstract & Authors:展开 Abstract:收起
Background and Purpose: Although human blood perfusion is largely redistributed into the mesenteric circulation after meals, the mechanisms by which postprandial nutrients induce mesenteric vasorelaxation, and whether this process is involved in the pathogenesis of colitis are not well understood. We aimed to study the direct actions of nutrients on mesenteric arterial tone and the underlying molecular mechanisms in healthy and colitis mice.
Experimental Approach: We used wire myograph and DSS‐induced colitis to investigate the roles and mechanisms of nutrient‐induced vasorelaxation of mesenteric arterioles from humans and mice. Ca2+ and Na+ imaging were also performed in human VEC and VSMC pre‐treated with selective pharmacological agents, and shRNA knockdown of TRPV1 channels.
Key Results: Glucose, sodium, and mannitol induced the endothelium‐dependent relaxation of human and mouse mesenteric arterioles via hyperosmotic action in a dose‐dependent manner. The hyperosmosis‐induced vasorelaxation was almost abolished by selective blockers for TRPV1, IKCa, and SKCa channels. Moreover, glucose markedly stimulated Ca2+ influx through endothelial TRPV1 channels, which was attenuated by selective blockers and the shRNA knockdown of TRPV1. Capsaicin synergised the glucose‐induced vasorelaxation. The nutrient‐induced hyperosmosis also activated NKA and NCX to further decrease [Ca2+]i in VSMC. Finally, the glucose‐induced vasorelaxation was impaired in mouse colitis.
Conclusion and Implications: Nutrient‐induced hyperosmosis evokes endothelium‐dependent mesenteric vasorelaxation via the TRPV1/Ca2+/EDH pathway to benefit normal mucosal perfusion, which is impaired in the pathogenesis of colitis. Our results suggest that the TRPV1/Ca2+/EDH pathway could provide novel potential drug targets for gastrointestinal diseases with hypoperfusion, such as chronic colitis and mesenteric ischemia.
First Authors:
Yanjun Guo,Cheng Lu Correspondence Authors:
Hui Dong All Authors:
Yanjun Guo,Cheng Lu,Luyun Zhang,Hanxing Wan,Enlai Jiang,Yao Chen,Hui Dong
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