Involvement of histamine in endothelium-dependent relaxation of mesenteric lymphatic vessels.

Involvement of histamine in endothelium-dependent relaxation of mesenteric lymphatic vessels.
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DOI:
10.1111/micc.12143
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发表时间:
2014-10
期刊:
Microcirculation (New York, N.Y. : 1994)
影响因子:
--
通讯作者:
Gashev AA
Gashev AA
中科院分区:
其他
文献类型:
--
作者:
Nizamutdinova IT;Maejima D;Nagai T;Bridenbaugh E;Thangaswamy S;Chatterjee V;Meininger CJ;Gashev AA

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淋巴功能的基本原理的知识,仍然是,在很大程度上,基本的,将需要大量的研究工作。最近的研究表明,肠系膜淋巴管(MLV)的生理存在的内皮源性舒张因子(EDRF)而不是一氧化氮。在这项研究中,我们测试的假设,淋巴内皮源性组胺放松MLV。我们在对照条件下以及用Nω-硝基-L-精氨酸甲酯盐酸盐(L-NAME,100 μM)或/和α-甲基-DL-组氨酸二盐酸盐(α-MHD,10 μM)药理学阻断一氧化氮和/或组胺产生后,测量和分析了离体和加压大鼠肠系膜淋巴管的淋巴收缩参数。α-MHD的有效性得到化学证实。我们还使用了组胺产生酶,组氨酸脱羧酶(HDC)的免疫组织化学标记和蛋白质印迹分析。此外,我们通过用体内吗啉代寡核苷酸瞬时转染来阻断MLV中的HDC蛋白表达。我们发现,只有一氧化氮和组胺产生的联合药理学阻断完全消除了淋巴管的流量依赖性松弛,从而证实了组胺在MLV中作为EDRF的作用。我们还证实了淋巴管内皮细胞内存在组氨酸脱羧酶和组胺。我们的研究支持组胺在MLV中作为EDRF的作用。
The knowledge of the basic principles of lymphatic function, still remains, to a large degree, rudimentary and will require significant research efforts. Recent studies of the physiology of the mesenteric lymphatic vessels (MLVs) suggested the presence of an endothelium-derived relaxing factor (EDRF) other than nitric oxide. In this study we tested the hypothesis that lymphatic endothelium-derived histamine relaxes MLVs. We measured and analyzed parameters of lymphatic contractility in isolated and pressurized rat mesenteric lymphatic vessels under control conditions and after pharmacological blockade of nitric oxide by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 μM) or/and histamine production by α-methyl-DL-histidine dihydrochloride (α-MHD, 10 μM). Effectiveness of α-MHD was confirmed immunohistochemically. We also used immunohistochemical labeling and western blot analysis of the histamine-producing enzyme, histidine decarboxylase (HDC). Additionally we blocked HDC protein expression in MLVs by transient transfection with vivo-morpholino oligos. We found that only combined pharmacological blockade of nitric oxide and histamine production completely eliminates flow-dependent relaxation of lymphatic vessels, thus confirming a role for histamine as an EDRF in MLVs. We also confirmed the presence of histidine decarboxylase and histamine inside lymphatic endothelial cells. Our study supports a role for histamine as an EDRF in MLVs.
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