Positive interaction between leukotriene C 4 and histamine and other mediators on vascular tissues

Abstract

The interaction of leukotriene C 4 (LTC 4) with the contractile activity of histamine (H), serotonin (5HT) and norepinephrine (NE) has been investigated in isolated vascular preparations. Threshold concentration of LTC 4 (5 × 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 LTC 4 had been washed. FPL-55712 (10 −5M) counteracted the increased H response on GPPA induced by LTC 4. Potentiation of H activity due to LTC 4 was also observed on guinea-pig thoracic aorta (GPTA) indicating that LTC 4-induced hyperreactivity is not a phenomenon restricted to the pulmonary vascular bed. In the experiments carried out in presence of indomethacin (3 × 10 −6M), LTC 4 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 LTC 4 These results demonstrate that LTC 4 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.