Leukotrienes C4 and D4 Are Potent Endothelium-Dependent Relaxing Agents in Canine Splanchnic Venous Capacitance Vessels

In the present study, the vasomotor effects of the peptide leukotrienes (LTs) LTC4 and LTD4 on isolated canine venous capacitance vessels were evaluated. Both LTs evoked marked concentration-dependent relaxation of norepinephrine-contracted rings of mesenteric and splenic veins and inferior vena cava but had minimal activity in the femoral vein. Relaxation induced by either LT was abolished after physical removal of the vascular endothelium, whereas marked relaxation responses were evoked by glyceryl trinitrate in the same endothelium-denuded rings. The nitric oxide synthase antagonist N-nitro-L-arginine methyl ester (L-NAME) completely abolished LT-induced mesenteric vein relaxation and unmasked a contractile effect of LTC4. Only partial attenuation of LT-induced relaxation of the inferior vena cava in the presence of L-NAME was observed. In the splenic vein, responses solely to LTC4 were very slightly reduced in the presence of L-NAME. Reduced hemoglobin (10 and 10 M) inhibited LTC4-evoked splenic vein relaxation and, in a concentration of 10 M, inhibited LTD4-evoked relaxation of the splenic vein. On the other hand, methylene blue (10 and 10 M) attenuated splenic vein relaxation produced by both LTs but solely reduced LTC4-evoked inferior vena cava relaxation. Thus, the peptide LTs, the major components of the slow-reacting substance of anaphylaxis, exert a profound endothelium-dependent relaxant effect on venous capacitance vessels, which is only partially dependent on L-arginine and nitric oxide. A role for LT-evoked capacitance venodilation as a mechanism contributing to the reduced venous return and cardiac output associated with systemic anaphylaxis is postulated.