Circulation Research, Vol 62, 983-991, Copyright © 1988 by American Heart Association

ARTICLES

Endothelial-dependent relaxation induced by leukotrienes C4, D4, and E4 in isolated canine arteries

RJ Secrest and BM Chapnick
Department of Pharmacology, St. Louis University School of Medicine, Missouri 63104.

Leukotriene D4 has been shown to possess the capacity to relax canine superior mesenteric and renal arterial rings in an endothelial- dependent manner. The present study was designed to determine if the remaining peptidoleukotrienes, leukotrienes C4 and E4, share this property. In addition, influences of atropine and of inhibitors of cyclooxygenase and lipoxygenase activities on relaxation produced by leukotriene D4 and acetylcholine were determined to characterize further leukotriene D4-induced relaxation and to compare these properties with those of acetylcholine. Vasomotor tone was measured with isometric force transducers. Following induction of tone with norepinephrine, leukotriene C4 and acetylcholine produced concentration- dependent relaxation of renal and superior mesenteric arterial rings in which the endothelium was intact. Only minimal decreases in tone were produced in response to leukotriene E4. Neither acetylcholine nor leukotriene C4 altered tone after endothelium had been intentionally disrupted. Nitroglycerin relaxed rings both before and after rubbing the endothelium. These results demonstrate that, similar to leukotriene D4, leukotriene C4 possesses the capacity to produce endothelial- dependent relaxation in canine renal and superior mesenteric arteries. Relaxation of the superior mesenteric artery produced in response to acetylcholine, but not leukotriene D4, was inhibited in presence of atropine. Incubation of the rings with meclofenamate had no effect on relaxation induced by either acetylcholine or leukotriene D4. Thus, it appears that endothelial-dependent relaxation induced by leukotriene D4 is neither dependent on muscarinic receptor activation nor related to generation of cyclooxygenase metabolites of arachidonic acid. In contrast, 5,8,11,14-eicosatetraynoic acid and nordihydroguaiaretic acid attenuated relaxation in response to leukotriene D4 and acetylcholine, suggesting that lipoxygenase-derived products may participate in leukotriene D4-induced as well as acetylcholine-induced relaxation.

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