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.
Lawson
D L
DL
Department of Medicine, University of Florida College of Medicine, Gainesville.
Mehta
J L
JL
Mehta
P
P
Nichols
W W
WW
D000098:Acetophenones / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D000098:Acetophenones; D002867:Chromones; D013189:SRS-A; D013777:Tetrazoles; D009569:Nitric Oxide; C044660:LY 171883; C006312:FPL 55712; D000109:Acetylcholine