Positive interaction between leukotriene C4 and histamine and other mediators on vascular tissues.

The interaction of leukotriene C4 (LTC4) with the contractile activity of histamine (H), serotonin (5HT) and norepinephrine (NE) has been investigated in isolated vascular preparations. Threshold concentration of LTC4 (5 X 10(-9) M) significantly potentiated the vasoconstricting effect of these compounds on guinea-pig pulmonary artery (GPPA). This phenomenon was long-lasting for H since it was still present 40 min after LTC4 had been washed. FPL-55712 (10(-5) M) counteracted the increased H response on GPPA induced by LTC4. Potentiation of H activity due to LTC4 was also observed on guinea-pig thoracic aorta (GPTA) indicating that LTC4-induced hyperreactivity is not a phenomenon restricted to the pulmonary vascular bed. In the experiments carried out in presence of indomethacin (3 X 10(-6) M), LTC4 still potentiated H-induced vasoconstriction on GPPA, however the time course of the phenomenon was significantly shorter than that observed in absence of the cyclooxygenase inhibitor. The contractile activity of H and NE on guinea-pig portal vein (GPPV) was not potentiated by LTC4. These results demonstrate that LTC4 induces hyperreactivity of the arterial vascular tissue to vasoactive compounds and suggest that cysteinyl-leukotrienes may have pathological significance in the hemodynamic changes occurring during anaphylactic reactions. Preliminary experiments carried out on human intralobar pulmonary artery strongly support this hypothesis.