Histamine as an Endothelium-Derived Relaxing Factor in Aged Mesenteric Lymphatic Vessels.
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BACKGROUND: 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. METHODS AND RESULTS: 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 N-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 100M) or/and blockade of histamine production by -methyl-DL-histidine dihydrochloride (-MHD, 10M). 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. CONCLUSIONS: 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.
