Beneficial effect of capsaicin via TRPV4/EDH signals on mesenteric arterioles of normal and colitis mice.

J Adv Res

Department of Pharmacology, School of Pharmacy, Qingdao University Medical College, #1 Ningde Road, Qingdao 266073, China; Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing 400037, China. Electronic address:

Published: July 2022

Introduction: Although capsaicin has long been used as food additive and medication worldwide, its actions on gastrointestinal tract as its most delivery pathway have not been well addressed.

Objectives: In the present study, we aimed to study GI actions of capsaicin on mesenteric arterioles in normal and colitis mice and to elucidate the underlying mechanisms.

Methods: Vasorelaxation of human submucosal arterioles and the mesenteric arterioles from wide-type (WT) mice, TRPV1 and TRPV4 (KO) mice were measured. The expression and function of TRPV channels in endothelial cells were examined by q-PCR, immunostaining, Ca imaging and membrane potential measurements.

Results: Capsaicin dose-dependently induced vasorelaxation of human submucosal arterioles and mouse mesenteric arterioles in vitro and in vivo through endothelium-dependent hyperpolarization (EDH), nitric oxide (NO), and prostacyclin (PGI). Using TRPV1 and TRPV4 KO mice, we found that capsaicin-induced vasorelaxation was predominately through TRPV4/EDH, but marginally through TRPV1/NO/PGI. Capsaicin induced hyperpolarization through activation of endothelial TRPV4 channels and intermediate-conductance of Ca-activated K channels to finally stimulate vasorelaxation. Importantly, capsaicin exerted anti-colitis action by rescuing the impaired ACh-induced vasorelaxation in WT colitis mice but not in TRPV4 KO colitis mice.

Conclusions: Capsaicin increases intestinal mucosal blood perfusion to potentially prevent/treat colitis through a novel TRPV4/EDH-dependent vasorelaxation of submucosal arterioles in health and colitis. This study further supports our previous notion that TRPV4/EDH in mesenteric circulation plays a critical role in the pathogenesis of colitis.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263647PMC
http://dx.doi.org/10.1016/j.jare.2021.11.001DOI Listing

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