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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our study supports a role for histamine as an EDRF in MLVs.