Flow-Mediated Release of Nitric Oxide from Lymphatic Endothelial Cells of Pressurized Canine Thoracic Duct

Abstract

We examined the effects of flow on lymphatic endothelial cells by using conventional cascade preparations of isolated coronary arteries without intact endothelium. The pressurized thoracic ducts were intraluminally perfused at a constant flow rate ranging from 0.5 to 2.0 ml/min. A linear relationship was observed between the flow rate and the normalized amount of relaxing substance(s) released from the lymphatic endothelial cells. Thus the flow rate of 2.0 ml/min produced ∼39% of sodium nitroprusside (SNP)–produced maximal relaxation in the cascade arterial rings. The acetylcholine (ACh, 10⁻⁵ M)- and flow-induced relaxations of the cascade arterial rings were completely reduced by the mechanical rubbing of lymphatic endothelial cells in the pressurized lymph vessels. Pretreatment with 5×10⁻⁵ M N^G-nitro-L-arginine methyl ester (L-NAME) on the lymphatic endothelial cells caused a significant reduction of the ACh- and flow-induced vasodilations of the cascade arterial rings. Pretreatment with 10⁻⁵ M indomethacin on the lymphatic endothelial cells produced no significant effect on the ACh- and flow-induced vasodilations. These findings suggest that lymphatic endothelial cells of canine thoracic ducts can produce and release endogenous nitric oxide by stimulation of flow (∼2.0 ml/min).