Nizamutdinova Irina Tsoy, Maejima Daisuke, Nagai Takashi, Meininger Cynthia J, Gashev Anatoliy A
1 Department of Medical Physiology, College of Medicine, Texas A&M University Health Science Center , Temple, Texas.
2 Department of Physiology, Shinshu University School of Medicine , Matsumoto, Japan .
Lymphat Res Biol. 2017 Jun;15(2):136-145. doi: 10.1089/lrb.2016.0062. Epub 2017 Apr 28.
Knowledge of the mechanisms by which aging affects contracting lymphatic vessels remains incomplete; therefore, the functional role of histamine in the reaction of aged lymphatic vessels to increases in flow remains unknown.
We measured and analyzed parameters of lymphatic contractility in isolated and pressurized rat mesenteric lymphatic vessels (MLVs) obtained from 9- and 24-month Fischer-344 rats under control conditions and after pharmacological blockade of nitric oxide (NO) by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 μM) or/and blockade of histamine production by α-methyl-DL-histidine dihydrochloride (α-MHD, 10 μM). We also quantitatively compared results of immunohistochemical labeling of the histamine-producing enzyme, histidine decarboxylase (HDC) in adult and aged MLVs. Our data provide the first demonstration of an increased functional role of histamine as an endothelial-derived relaxing factor in aged MLVs, which appears in parallel with the abolished role of NO in the reactions of these lymph vessels to increases in flow. In addition, we found an increased expression of HDC in endothelium of aged MLVs.
Our findings provide the basis for better understanding of the processes of aging in lymphatic vessels and for setting new important directions for investigations of the aging-associated disturbances in lymph flow and the immune response.
衰老影响淋巴管收缩的机制尚不完全清楚；因此，组胺在衰老淋巴管对流量增加的反应中的功能作用仍然未知。
我们测量并分析了从9个月和24个月大的Fischer-344大鼠分离并加压的肠系膜淋巴管（MLV）在对照条件下以及在用盐酸Nω-硝基-L-精氨酸甲酯（L-NAME，100 μM）药理学阻断一氧化氮（NO）或/和用盐酸α-甲基-DL-组氨酸（α-MHD，10 μM）阻断组胺产生后的淋巴管收缩参数。我们还定量比较了成年和老年MLV中产生组胺的酶——组氨酸脱羧酶（HDC）的免疫组织化学标记结果。我们的数据首次证明了组胺作为一种内皮源性舒张因子在老年MLV中的功能作用增强，这与NO在这些淋巴管对流量增加的反应中的作用消失同时出现。此外，我们发现老年MLV内皮中HDC的表达增加。
我们的研究结果为更好地理解淋巴管衰老过程以及为研究与衰老相关的淋巴流动和免疫反应紊乱设定新的重要方向提供了基础。
