title: Positive interaction between leukotriene C4 and histamine and other mediators on vascular tissues.
abstract: 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.
mesh_terms: D000707:Anaphylaxis / Q000209:etiology / Q000503:physiopathology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004357:Drug Synergism; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects; D011651:Pulmonary Artery / Q000187:drug effects; D013189:SRS-A / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D002867:Chromones; D013189:SRS-A; D012701:Serotonin; D006632:Histamine; C006312:FPL 55712; D009638:Norepinephrine