Suppression of lymphatic vessel contractility with inhibitors of arachidonic acid metabolism.

Contractions of lymphatic vessels play an important role in regulating lymph flow; however, little is known of the pharmacological properties of these vessels and the mechanisms regulating the contractions. Earlier work had suggested that arachidonic acid metabolites may play some role in the contractile process and in this report we have assessed the effects of various inhibitors of arachidonate metabolism on the contractions of bovine mesenteric lymphatic rings suspended in tissue baths. Aspirin and indomethacin (cyclooxygenase inhibitors), BW 755C (a cyclooxygenase and lipoxygenase inhibitor) and FPL 55712 (a slow reacting substance of anaphylaxis-leukotriene-antagonist) suppressed the phasic contractions of spontaneously active vessels. The addition of arachidonate to noncontracting vessels elicited phasic and tonic contractile activities which were similarly blocked with these drugs, as were the contractions elicited with several agonists. These results suggest that lymphatic vessel contractions are extremely susceptible to suppression with inhibitors of arachidonate metabolism implying that these drugs may alter extravascular fluid dynamics by a direct effect on the lymphatic vessel. The intrinsic contractile regulatory mechanism may involve the production of arachidonate products within the vessel.