Lymphatic smooth muscle responses to leukotrienes, histamine and platelet activating factor

Regional lymphatics regulate the accumulation of edema resulting from inflammation. The effects of mediators of inflammation on lymphatic smooth muscle, the primary determinant of lymph flow, are poorly understood. We studied mesenteric lymphatic vessels in 22 anesthetized rats with in vivo videomicroscopy following topical applications of histamine, leukotriene C4 or D4, or platelet-activating factor (PAF). Diameter, contractility, and contraction frequency were measured, and flow was calculated. Histamine caused increases in vessel diameter and contractility (174 and 218% of control, respectively; P less than 0.05), while contraction frequency was unaffected. Leukotrienes C4 and D4 caused an increase in frequency of contraction (348 and 392% of control, respectively; P less than 0.05), while having no significant influence on diameter or contractility. PAF caused smooth muscle relaxation, resulting in vasodilation and a decrease in contraction frequency (202 and 5% of control, respectively; P less than 0.05). Topical application of histamine and leukotrienes caused significant increases in calculated flow, while PAF decreased calculated flow. Mediators of inflammation have striking and diverse effects on lymphatic smooth muscle activity.