Histamine is novel endothelium‐derived relaxing factor in rat mesenteric lymphatic vessels

Abstract

Our recent studies (Nagai et al., 2011) suggested the existence of yet undiscovered, shear‐dependent, but NO‐independent regulatory mechanism in rat mesenteric lymphatic vessels (MLV). In this study we performed for the first time the detailed evaluation of potential involvement of histamine in such regulation of MLV contractility in F‐344 rats of various age groups (3‐mo, 9‐mo and 24‐mo). Using confocal and epifluorescent IHC labeling, we confirmed the presence of histidine decarboxylase (HDC), histamine‐producing enzyme, within the lymphatic endothelial cells in MLV. These results were re‐confirmed by Western blot analysis. Using Vivo‐Morpholino technology we were able to knock‐down effectively HDC protein within MLV. In experiments with isolated MLV, we found that only combined blockade of eNOS (NO production) by L‐NAME and HDC (histamine production) by α‐methyl‐DL‐histidine dihydrochloride was able to completely eliminate all shear‐dependency of lymphatic contractile self‐adjustment during periods of steady increases of imposed flow. Such regulatory role of histamine appears to be not severely altered by aging. Up‐to‐date results shows that histamine is not involved in fast phasic contraction‐generated shear‐dependent contractile regulation. Our data provide ground for new understanding on the role of histamine in regulation of lymphatic function. NIH R01 AG030578, HL094269.