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BA Berkowitz, B Zabko-Potapovich, R Valocik and JG Gleason
We have examined in these studies the contractile activity of leukotrienes (LTs) C4, D4 and E4 on vascular ring segments obtained from several species and demonstrated that the distal segment of the guinea-pig pulmonary artery is a useful and convenient preparation for the study of LT vascular pharmacology. In vitro, LTs had no effect on aortic rings from rats, rabbits or guinea pigs. In contrast, LTs produced significant contraction of the distal portion of the pulmonary artery of the guinea pig. The rank of the contractile effects of LT was LTD4 = LTC4, greater than LTE4, with ED40 (molar) values of 6.1 X 10(- 9), 1 X 10(-8) and 1.4 X 10(-6), respectively. Norepinephrine, serotonin and histamine were at least 50- to 100-fold less potent. Partial tolerance developed to the contractile action of LT in vitro. Vascular contraction produced by LTD4 was antagonized by a selective LT antagonist. No evidence for a relaxant action of LT was obtained as LTD4 and LTC4 failed to relax rabbit aorta or guinea-pig pulmonary arterial rings. The effects of LTD4 on hemodynamics in vivo were studied in anesthetized guinea pigs. LTD4 (0.1-10 micrograms/kg) significantly decreased cardiac output but increased pulmonary vascular resistance. To assess the activity of LTs in another species, the in vitro contractile response of monkey pulmonary artery was determined. LTD4 was also a potent contractile agent in this species with significant contraction obtained at 1 X 10(-9) M.(ABSTRACT TRUNCATED AT 250 WORDS)
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