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To characterize the influences of leukotriene D4 on regional vascular smooth muscle, effects of leukotriene D4 on vasomotor tone of canine renal and superior mesenteric arterial rings were determined. Vascular smooth muscle tone was measured with isometric force transducers. After tone had been induced with norepinephrine, leukotriene D4, in concentrations of 10(-8) M to 10(-7) M, produced dose-dependent relaxation of renal and superior mesenteric arterial rings. Leukotriene D4-induced relaxation was observed only in those ring preparations in which care had been taken to avoid damaging the luminal surface. Acetylcholine (10(-7) M) also decreased tone in these same ring segments. Neither acetylcholine nor leukotriene D4 altered tone of arterial rings after the endothelium had been intentionally disrupted by rubbing with a cotton-tipped applicator. Nitroglycerin (10(-6) M) relaxed rings both before and after rubbing the intimal surface. These results demonstrate that leukotriene D4 possesses the capacity to relax canine superior mesenteric and renal arterial rings in an endothelial-dependent manner. Because relaxation of renal and superior mesenteric arterial rings in response to leukotriene D4 was not altered after incubation with indomethacin (10(-5) M), the observed endothelial-dependent relaxation induced by leukotriene D4 did not appear to be related to release of a cyclooxygenase metabolite(s). In contrast, FPL 55712 (10(-5) M) attenuated the relaxation produced by leukotriene D4, suggesting that this response was a receptor-linked consequence.

Leukotriene D4 relaxes canine renal and superior mesenteric arteries.