Endothelium-dependent relaxation of rat aortic rings by leukotriene D4: importance of the magnitude of preload.

Leukotriene D4 (LTD4) generally constricts vascular smooth muscle resulting in reduction in blood flow in a variety of blood vessels which can be blocked by specific LT-receptor antagonists. LTD4 has also been shown to cause vasodilation in some animal species. To examine the basis of vasodilation, we evaluated the effects of LTD4 (10(-9) to 2 X 10(-6) M) on precontracted rat thoracic aortic rings in a tissue bath. LTD4 caused relaxation of the rat thoracic rings in a concentration-dependent fashion. This relaxant effect of LTD4 on rat aortic rings was observed regardless of the stimulus used for precontraction, such as l-epinephrine, l-norepinephrine, KCl, 5-hydroxy-tryptamine, or non-pharmacologic manual stretch. This relaxant effect of LTD4 was not blocked by inhibition of vascular eicosanoid synthesis with indomethacin or LT-receptor blockade with two different agents FPL-55712 or LY171883. However, de-endothelialization of rat thoracic aortic rings or treatment of aortic rings with the 5-lipoxygenase inhibitor nordihydroguaiaretic acid abolished the relaxant effect of LTD4. In addition, pretreatment of rings with an inhibitor of endothelium-derived relaxing factor (EDRF), free hemoglobin, also resulted in inhibition of LTD4-induced vascular relaxation. These observations suggest that the rat aortic ring relaxation by LTD4 is endothelium-dependent and is probably related to the release of EDRF.