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

作者全名："Zhang, Luyun; Lu, Wei; Lu, Cheng; Guo, Yanjun; Chen, Xiongying; Chen, Jun; Xu, Feng; Wan, Hanxing; Dong, Hui"

作者地址："[Lu, Wei; Dong, Hui] Qingdao Univ, Sch Pharm, Dept Pharmacol, Med Coll, 1 Ningde Rd, Qingdao 266073, Peoples R China; [Zhang, Luyun; Chen, Xiongying; Xu, Feng; Wan, Hanxing] Chongqing Med Univ, Dept Pediat Intens Care Unit, Childrens Hosp, Chongqing 400014, Peoples R China; [Lu, Cheng; Guo, Yanjun; Chen, Jun; Wan, Hanxing; Dong, Hui] Army Med Univ, Xinqiao Hosp, Dept Gastroenterol, Chongqing 400037, Peoples R China; [Wan, Hanxing; Dong, Hui] Qingdao Univ, Sch Pharm, Dept Pharmacol, Med Coll, 1 Ningde Rd, Qingdao 266073, Peoples R China"

通信作者："Wan, HX; Dong, H (通讯作者)，Qingdao Univ, Sch Pharm, Dept Pharmacol, Med Coll, 1 Ningde Rd, Qingdao 266073, Peoples R China."

来源：JOURNAL OF ADVANCED RESEARCH

ESI学科分类：Multidisciplinary

WOS号：WOS:000822618000001

JCR分区：Q1

影响因子：10.7

年份：2022

卷号：39

期号：　

开始页：291

结束页：303

文献类型：Article

关键词：Submucosal arterioles; Endothelium-derived hyperpolarization; TRPV4 channels; Colitis

摘要："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, Ca2+ 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(2)). Using TRPV1 and TRPV4 KO mice, we found that capsaicin-induced vasorelaxation was predominately through TRPV4/EDH, but marginally through TRPV1/NO/PGI(2). Capsaicin induced hyperpolarization through activation of endothelial TRPV4 channels and intermediate-conductance of Ca2+-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. (c) 2022 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)."

基金机构："National Key Research and Development Program of China [2016YFC1302200]; National Natural Science Foundation of China [81873544, 81972328]"

基金资助正文："Acknowledgements This work were supported by research grants from the National Key Research and Development Program of China (No. 2016YFC1302200 to HD) , the National Natural Science Foundation of China (No. 81873544 to HD and 81972328 to HW) , and the start-up funding of QDU."