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Nutrient-induced hyperosmosis evokes vasorelaxation via TRPV1-mediated endothelium-dependent hyperpolarization in normal and colitis mice
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  • Yanjun Guo,
  • Cheng Lu,
  • Luyun Zhang,
  • Hanxing Wan,
  • Enlai Jiang,
  • Yao Chen,
  • Hui Dong
Yanjun Guo
Xinqiao Hospital, Army Medical University

Corresponding Author:[email protected]

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Cheng Lu
Xinqiao Hospital, Army Medical University
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Luyun Zhang
Xinqiao Hospital, Army Medical University
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Hanxing Wan
Xinqiao Hospital, Army Medical University
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Enlai Jiang
Xinqiao Hospital, Army Medical University
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Yao Chen
Xinqiao Hospital, Army Medical University
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Hui Dong
University of California, San Diego
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Background and Purpose: Although human blood flows are redistributed into the mesenteric circulation after meals, it is not well understood how postprandial nutrients induces vasorelaxation of mesenteric micro-arterioles and whether this process is involved in the pathogenesis of colitis.  Experimental Approach: We used an auto dual wire myograph system, fluorescence imaging system and DSS-induced colitis mouse model to investigate the roles and mechanisms of nutrient-induced mesenteric relaxation in health and disease. Key Results: We found that acute application of glucose and sodium induced endothelium-dependent relaxation of human and mouse mesenteric micro-arterioles via a hyperosmotic action, which also stimulated Ca2+ influx through endothelial TRPV1 channels. The nutrient-induced vasorelaxation was almost abolished by selective blockers for TRPV1, IKCa and SKCa channels, but marginally altered by inhibition of nitric oxide production. The nutrient-induced hyperosmosis also activated functional activities of Na+/K+-ATPase and Na+/Ca2+-exchanger to further reduce [Ca2+]i in vascular smooth muscle cells. Moreover, hyperosmosis-induced endothelium-dependent hyperpolarization was significantly impaired in colitis mouse model. Conclusion and Implications: Our study provides the first evidence that nutrient-induced hyperosmosis stimulates endothelial TRPV1/Ca2+/EDH signaling pathway to eventually evoke vasorelaxation of mesenteric micro-arterioles, which may contribute to the pathogenesis of colitis as well.
12 May 2020Submitted to British Journal of Pharmacology
14 May 2020Submission Checks Completed
14 May 2020Assigned to Editor
14 May 2020Reviewer(s) Assigned
08 Jun 2020Editorial Decision: Revise Minor
06 Sep 20201st Revision Received
06 Sep 2020Submission Checks Completed
06 Sep 2020Assigned to Editor
07 Sep 2020Reviewer(s) Assigned
23 Sep 2020Review(s) Completed, Editorial Evaluation Pending
27 Sep 2020Editorial Decision: Revise Minor
11 Oct 20202nd Revision Received
12 Oct 2020Submission Checks Completed
12 Oct 2020Assigned to Editor
13 Oct 2020Reviewer(s) Assigned
22 Oct 2020Review(s) Completed, Editorial Evaluation Pending
29 Oct 2020Editorial Decision: Accept