Cyclopiazonic Acid-Induced Ca(2+) Store Depletion Initiates Endothelium-Dependent Hyperpolarization-Mediated Vasorelaxation of Mesenteric Arteries in Healthy and Colitis Mice.
Cyclopiazonic Acid-Induced Ca(2+) Store Depletion Initiates Endothelium-Dependent Hyperpolarization-Mediated Vasorelaxation of Mesenteric Arteries in Healthy and Colitis Mice.
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环匹阿尼酸诱导的 Ca2+ 储存消耗启动健康小鼠和结肠炎小鼠中内皮依赖性超极化介导的肠系膜动脉血管舒张
DOI：
10.3389/fphys.2021.639857
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发表时间：
2021
影响因子：
4
通讯作者：
Xu F
中科院分区：
文献类型：
--
作者：
Zhang LY;Chen XY;Dong H;Xu F
用途：由于钙库操纵的钙内流（SOCE）在健康和结肠炎中内皮依赖性超极化（EDH）介导的肠系膜动脉血管舒张中的作用尚不完全清楚，因此使用肌浆网钙ATP酶（SERCA）的特异性抑制剂环匹阿尼酸（CPA）作为SOCE激活剂来研究其在正常小鼠中的作用和在结肠炎小鼠中的改变。研究方法：应用单细胞钙离子成像技术检测血管内皮细胞（VEC）内钙离子信号的变化，应用丹麦DMT 520 A微血管测量系统检测CPA对肠系膜动脉张力的影响。结果：CPA通过消耗内皮细胞内质网内Ca 2+激活SOCE。CPA在内皮完整的肠系膜动脉中具有浓度依赖性的血管舒张作用，去除内皮后该作用丧失。一氧化氮（NO）和前列环素（PGI 2）抑制剂对CPA诱导的血管舒张无影响;然而，在NO和PGI 2被抑制后，KCa通道阻断剂[10 mM四乙基氯化铵（TEA）]抑制CPA诱导的血管舒张，而KCa通道激活剂两种SOCE阻断剂[30 μM SKF 96365和100 μM氟灭酸（FFA）]和一种奥赖通道阻断剂（30 μM GSK-7975 A）抑制这种血管舒张作用。抑制Na+/K+-ATP酶（NKA）和Na+/Ca ~（2+）交换（NCX）也可抑制CPA的舒张作用。最后，CPA参与EDH诱导的血管舒张的消耗ER Ca 2+的肠系膜动脉在结肠炎小鼠受损。总结：CPA耗竭ER Ca ~（2+）引起肠系膜动脉舒张，这是通过EDH机制介导的，并激活SOCE。CPA诱导的内皮依赖性扩张在结肠炎中受损，这可能限制肠粘膜的血液灌注。
Purposes: Since the role of store-operated calcium entry (SOCE) in endothelium-dependent hyperpolarization (EDH)-mediated vasorelaxation of mesenteric arteries in health and colitis is not fully understood, cyclopiazonic acid (CPA), a specific inhibitor of the sarco(endo) plasmic reticulum calcium-ATPases (SERCA), was used as a SOCE activator to investigate its role in normal mice and its alteration in colitis mice. Methods: The changes in Ca2+ signaling in vascular endothelial cells (VEC) were examined by single cell Ca2+ imaging and tension of mesenteric arteries in response to CPA were examined using Danish DMT520A microvascular measuring system. Results: CPA activated the SOCE through depletion of the endoplasmic reticulum (ER) Ca2+ in endothelial cells. CPA had a concentration-dependent vasorelaxing effect in endothelium-intact mesenteric arteries, which was lost after endothelial removal. Both nitric oxide (NO) and prostacyclin (PGI2) inhibitors did not affect CPA-induced vasorelaxation; however, after both NO and PGI2 were inhibited, KCa channel blocker [10 mM tetraethylammonium chloride (TEA)] inhibited CPA-induced vasorelaxation while KCa channel activator (0.3 μM SKA-31) promoted it. Two SOCE blockers [30 μM SKF96365 and 100 μM flufenamic acid (FFA)], and an Orai channel blocker (30 μM GSK-7975A) inhibited this vasorelaxation. The inhibition of both Na+/K+-ATPase (NKA) and Na+/Ca2+-exchange (NCX) also inhibited CPA-induced vasorelaxation. Finally, the CPA involved in EDH-induced vasorelaxation by the depletion of ER Ca2+ of mesenteric arteries was impaired in colitis mice. Conclusion: Depletion of ER Ca2+ by CPA induces a vasorelaxation of mesenteric arteries that is mediated through EDH mechanism and invokes the activation of SOCE. The CPA-induced endothelium-dependent dilation is impaired in colitis which may limit blood perfusion to the intestinal mucosa.
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影响因子：
5.5
作者：
Dedkova, EN;Blatter, LA
通讯作者：
Blatter, LA
DOI：
10.1161/atvbaha.108.172692
发表时间：
2008-10-01
影响因子：
8.7
作者：
Edwards, David H.;Li, Yiwen;Griffith, Tudor M.
通讯作者：
Griffith, Tudor M.
影响因子：
7.3
作者：
Gluais, P;Edwards, G;Félétou, M
通讯作者：
Félétou, M
DOI：
10.1161/01.atv.14.11.1821
发表时间：
1994-11-01
期刊：
ARTERIOSCLEROSIS AND THROMBOSIS
影响因子：
--
作者：
KRUSE, HJ;GRUNBERG, B;WEBER, PC
通讯作者：
WEBER, PC
营养诱导的高渗通过 TRPV1 通道介导的内皮依赖性超极化在健康小鼠和结肠炎小鼠中引起血管舒张
影响因子：
7.3
作者：
Guo, Yanjun;Lu, Cheng;Dong, Hui
通讯作者：
Dong, Hui