Article date: December 1988
By: H.B. Yaacob, Priscilla J. Piper in Volume 95, Issue 4, pages 1322-1328
Ovalbumen (100μg)‐induced coronary vasoconstriction and decrease in cardiac developed tension were studied in isolated perfused hearts from sensitized guinea‐pigs. Leukotriene‐like material released in the cardiac effluent was assayed against synthetic leukotriene C4 (LTC4).
LTC4 was released in a time‐dependent fashion, and release was enhanced when hearts were challenged in the presence of indomethacin (2.8 μm). The release was maximal at 2–3 min and detectable for as long as 10 min following ovalbumen challenge. Immunoreactive (ir) thromboxane‐B2 (TxB2) was also detected in cardiac effluent which had been partially purified using C18 Sep‐Paks.
CGS 8515 (0.03–1.0 μm), an inhibitor of 5‐lipoxygenase, dose‐dependently inhibited ovalbumen‐induced coronary vasoconstriction and leukotriene‐C4 release. CGS 8515 inhibited ovalbumen‐induced decreases in cardiac developed tension at 0.3 and 1.0 μm, but did not antagonize coronary vasoconstriction induced by synthetic LTC4.
The release of cyclo‐oxygenase products following ovalbumen challenge was not inhibited by CGS 8515, but was markedly inhibited by indomethacin (2.8 μm) pretreatment.
We conclude that leukotrienes have a major role in guinea‐pig cardiac anaphylaxis, and that CGS 8515 has a cardio‐protective action. The results obtained in these experiments in vitro show that CGS 8515 is a potent and selective 5‐lipoxygenase inhibitor.
Ovalbumen (100μg)‐induced coronary vasoconstriction and decrease in cardiac developed tension were studied in isolated perfused hearts from sensitized guinea‐pigs. Leukotriene‐like material released in the cardiac effluent was assayed against synthetic leukotriene C4 (LTC4).
LTC4 was released in a time‐dependent fashion, and release was enhanced when hearts were challenged in the presence of indomethacin (2.8 μm). The release was maximal at 2–3 min and detectable for as long as 10 min following ovalbumen challenge. Immunoreactive (ir) thromboxane‐B2 (TxB2) was also detected in cardiac effluent which had been partially purified using C18 Sep‐Paks.
CGS 8515 (0.03–1.0 μm), an inhibitor of 5‐lipoxygenase, dose‐dependently inhibited ovalbumen‐induced coronary vasoconstriction and leukotriene‐C4 release. CGS 8515 inhibited ovalbumen‐induced decreases in cardiac developed tension at 0.3 and 1.0 μm, but did not antagonize coronary vasoconstriction induced by synthetic LTC4.
The release of cyclo‐oxygenase products following ovalbumen challenge was not inhibited by CGS 8515, but was markedly inhibited by indomethacin (2.8 μm) pretreatment.
We conclude that leukotrienes have a major role in guinea‐pig cardiac anaphylaxis, and that CGS 8515 has a cardio‐protective action. The results obtained in these experiments in vitro show that CGS 8515 is a potent and selective 5‐lipoxygenase inhibitor.
DOI: 10.1111/j.1476-5381.1988.tb11771.x
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