Beneficial effect of capsaicin via TRPV4/EDH signals on mesenteric arterioles of normal and colitis mice.
Beneficial effect of capsaicin via TRPV4/EDH signals on mesenteric arterioles of normal and colitis mice.
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辣椒素通过 TRPV4/EDH 信号对正常和结肠炎小鼠肠系膜小动脉的有益作用
DOI：
10.1016/j.jare.2021.11.001
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发表时间：
2022-07
影响因子：
10.7
通讯作者：
Dong, Hui
中科院分区：
文献类型：
--
作者：
Zhang, Luyun;Lu, Wei;Lu, Cheng;Guo, Yanjun;Chen, Xiongying;Chen, Jun;Xu, Feng;Wan, Hanxing;Dong, Hui
辣椒素诱导离体人结肠粘膜下小动脉血管舒张的实验研究。辣椒素诱导人粘膜下小动脉内皮依赖性血管舒张。辣椒素诱导小鼠肠系膜小动脉内皮依赖性血管舒张。辣椒素通过TRPV 1介导的内皮细胞一氧化氮释放轻微地诱导血管舒张。辣椒素主要通过TRPV 4/内皮依赖性超极化引起血管舒张。辣椒素在野生型小鼠中具有抗结肠炎作用，但在TRPV 4基因敲除小鼠中没有。辣椒素通过TRPV 4/EDH通路挽救受损的内皮依赖性血管舒张。辣椒素作为食品添加剂和药物已在世界范围内得到广泛应用，但其在胃肠道中的作用尚未得到很好的研究。在本研究中，我们的目的是研究辣椒素对正常和结肠炎小鼠肠系膜小动脉的胃肠道作用，并阐明其潜在的机制。测量人粘膜下小动脉和野生型（WT）小鼠、TRPV 1 −/−和TRPV 4 −/−（KO）小鼠肠系膜小动脉的血管舒张。采用q-PCR、免疫组化、钙离子成像和膜电位测定等方法检测内皮细胞TRPV通道的表达和功能。辣椒素通过内皮依赖性超极化（EDH）、一氧化氮（NO）和前列环素（PGI 2）在体外和体内剂量依赖性地诱导人粘膜下小动脉和小鼠肠系膜小动脉的血管舒张。使用TRPV 1和TRPV 4 KO小鼠，我们发现辣椒素诱导的血管舒张主要通过TRPV 4/EDH，但也有少量通过TRPV 1/NO/PGI 2。辣椒素通过激活内皮TRPV 4通道和介导Ca ~（2+）激活的K ~+通道诱导超极化，最终刺激血管舒张。重要的是，辣椒素通过挽救WT结肠炎小鼠中受损的ACh诱导的血管舒张而发挥抗结肠炎作用，但在TRPV 4 KO结肠炎小鼠中没有。辣椒素增加肠粘膜血液灌流，通过健康和结肠炎中粘膜下小动脉的新型TRPV 4/EDH依赖性血管松弛作用，有可能预防/治疗结肠炎。本研究进一步支持了我们先前的观点，即肠系膜循环中的TRPV 4/EDH在结肠炎的发病机制中起着关键作用。
Capsaicin induced vasorelaxation of human colonic submucosal arterioles in vitro and in vitro. Capsaicin induced an endothelium-dependent vasorelaxation of human submucosal arterioles. Capsaicin induced an endothelium-dependent vasorelaxation of mouse mesenteric arterioles. Capsaicin induced vasorelaxation minily by TRPV1-mediated endothelial nitric oxide release. Capsaicin induced vasorelaxation mainly by TRPV4/endothelium-dependent hyperpolarization. Capsaicin exerted anti-colitis action in wide-type mice, but not in TRPV4 knock-out mice. Capsaicin rescued the impaired endothelium-dependent vasorelaxation via TRPV4/EDH pathway. 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. 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. 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. 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 (PGI2). Using TRPV1 and TRPV4 KO mice, we found that capsaicin-induced vasorelaxation was predominately through TRPV4/EDH, but marginally through TRPV1/NO/PGI2. 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. 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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影响因子：
64.8
作者：
Gao X;Zhang D;Xu C;Li H;Caron KM;Frenette PS
通讯作者：
Frenette PS
影响因子：
30.5
作者：
Bertin S;Aoki-Nonaka Y;de Jong PR;Nohara LL;Xu H;Stanwood SR;Srikanth S;Lee J;To K;Abramson L;Yu T;Han T;Touma R;Li X;González-Navajas JM;Herdman S;Corr M;Fu G;Dong H;Gwack Y;Franco A;Jefferies WA;Raz E
通讯作者：
Raz E
影响因子：
29.4
作者：
HOLZER, P;PABST, MA;LIPPE, IT
通讯作者：
LIPPE, IT
影响因子：
7.7
作者：
Chan WC;Millwood IY;Kartsonaki C;Du H;Guo Y;Chen Y;Bian Z;Walters RG;Lv J;He P;Hu C;Li L;Yang L;Chen Z;China Kadoorie Biobank (CKB) Collaborative Group
通讯作者：
China Kadoorie Biobank (CKB) Collaborative Group
DOI：
10.1152/ajpgi.00114.2007
发表时间：
2007-10-01
影响因子：
4.5
作者：
Eijkelkamp, Niels;Kavelaars, Annemieke;Heijnen, Cobi J.
通讯作者：
Heijnen, Cobi J.