Peptidoleukotrienes induce an endothelium-dependent relaxation of guinea pig main pulmonary artery and thoracic aorta.

The purpose of our investigation was to assess the role of the endothelium in the vasomotor effects of leukotrienes. Norepinephrine-preconstricted rings isolated from guinea pig main pulmonary artery and thoracic aorta responded to LTC4 and LTD4 with a concentration-dependent relaxation. In endothelium-denuded rings, both LTC4 and LTD4 caused a concentration-dependent contraction. The LTD4 receptor antagonist ICI 198,615 inhibited both LTC4- and LTD4-induced relaxation and contraction. Inhibition of gamma-glutamyl transpeptidase with AT-125 prevented the effects of LTC4, but not those of LTD4. The relaxant effect of LTD4 was not modified by indomethacin, but was abolished by methylene blue. We conclude that: 1) LTD4 induces a receptor-mediated endothelium-dependent relaxation of cavian pulmonary artery and aorta; 2) the vasorelaxant effect of LTC4 requires its conversion to LTD4; 3) the vasorelaxant effect of LTD4 is unrelated to PGI2 release, and is probably due to the release of an "EDRF"; 4) the removal of the endothelium reveals a direct receptor-mediated vasoconstricting effect of leukotrienes.