The direct and indirect actions of two active components of slow-reacting substance of anaphylaxis, leukotrienes C4 (LTC4) and D4 (LTD4), were studied in chronically instrumented unanesthetized sheep. Intravenous injection of 3 μ g of LTD4 caused immediate marked pulmonary arterial hypertension which returned to baseline in 6.5 ± 1.0 min. Dynamic compliance of the lungs (Cdyn) and left atrial (PLA) and aortic (Paorta) blood pressure fell concomitantly with the increases in pulmonary artery pressure (PPA)· PLA and Paorta then increased above baseline and heart rate decreased significantly. LTD4 caused only small increases in lung lymph flow but did increase lung lymph concentrations of thromboxane B2. Lung lymph concentrations of 6-keto-prostaglandin F1α did not increase following LTD4 infusion. The increase in PPA after 3-μ g injections of LTD4 was greater than that caused by 10-μ g injections of prostaglandin H2-analog. Injections of 10–30 μ g of LTC4 caused only minor increases in PPA but did cause bradycardia and delayed increases in PLA and Paorta· The cyclooxygenase inhibitors meclofenamate and ibuprofen inhibited the increases in PPA caused by LTD4 but not the later bradycardia or increases in PLA and Paorta· The thromboxane synthetase inhibitor UK-38485 attenuated the early increase in PPA and moderated the later increases in PLA and Paorta and bradycardia caused by LTD4 injection. The response of unanesthetized sheep to LTD4 is mediated, at least in part, indirectly by stimulation of the cyclooxygenase pathway of arachidonate metabolism.

Keywords:
Pulmonary dysfunction, Slow-reacting substance of anaphylaxis, Arachidonate, Cyclooxygenase, Thromboxane
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© 1987 S. Karger AG, Basel
1987
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