LTC4 Induces Hyperreactivity of the Isolated Vascular Tissue to Histamine, Serotonin and Norepinephrine
Leukotrienes (LTs) are released from human lung “in vitro” 1’2 and they exert a potent bronshocontracturating activity in normal and asthmatic subjects3, suggesting an important role for LTs in the allergic bronchoconstriction4. On the other hand anaphylactic shock is accompanied by increase in pulmonary vascular resistance5 and both specific antigen-challenge and LTs “in vitro” induce a vasoconstriction of pulmonary vessels of different animal species6,7. During anaphylactic reaction the vessels of the respiratory system release a considerable amount of LTD4 8,9 and its relative low pharmacological activity10 in this vascular tissue does not rule out a possible interaction with other chemical mediators. All these observations prompted us to investigate the ability of LTs to induce vascular hyperreactivity to other vasoactive compounds. In this regard LTs have been suggested to play a role in the pathogenesis of bronchial hyperreactivity11,12; in addition to this, Creese and Bach13 have shown in guinea-pig tracheal smooth muscle a clear cut potentiating action of LTD4 on histamine and acetylcholine induced contractions.
KeywordsContractile Activity Pulmonary Vessel Organ Bath Constrictive Effect Vasoactive Compound
Unable to display preview. Download preview PDF.
- 2).G. C. Folco. Pharmacological studies on the release and effects of leukotrienes in human and guinea-pig lung tissue. Submitted Iuphar 9th International Congress of Pharmacology Macmillans Press. Ltd.Google Scholar
- 3).M. Griffin, J. Woodrow Weiss, A. Gordon Heitch, E.R. McFadden, E.J. Corey, K.F. Austen and J.M. Drazen. Effects of leukotriene D on the airways in asthma. New Eng. J. Med. 308 (8): 436, 1983.Google Scholar
- 4).B. Samuelsson. The leukotrienes: Mediators of Immediate Hypersensitivity Reactions and Inflammation. in: Leukotrienes and Prostacyclin. Ed: F. Berti, G. Folco and G.P. Velo. Plenum Press p. 15, 1983.Google Scholar
- 5).W. E. Brocklehurst: The release of histamine and formation of a slow reacting substance (SRS-A) during anaphylactic shock. J. Physiol (Lond) 151: 416, 1960.Google Scholar
- 7).P. Eyre. The Schultz-Dale reaction in bovine pulmonary smooth muscles. Br. J. Pharmacol 40: 166p, 1970.Google Scholar
- 8).J. H. Fleisch and K.D. Haisch. Release of slow reacting substance from various tissues by A23187. J. Pharm. Pharmacol. 34: 809, 1982Google Scholar
- 10).J. M. Hand, J.A. Will and C.L. Buckner. Effects of leukotrienes on isolated guinea-pig pulmonary arteries. Eur. J. Pharmacol. 76: 439, 1981.Google Scholar
- 12).D. S. Dhillon, I.W. Rodger. Hyperreactivity of guinea-pig isolated airway smooth muscle. Br. J. Pharmacol. 74: 180P, 1981.Google Scholar
- 14).Sneidecor and Cochran. Factorial experiments in: “Statistical Methods VI” Ed. IOWA State University Press AMES. IOWA USA p. 339, 1967.Google Scholar
- 15).S. H. Ferreira and F.S. De Souza-Costa. A laminar flow superfusion technique with much increased sensitivity for the detection of smooth muscle stimulating substances. Eur. J. Pharmac. 39: 379, 1976.Google Scholar
- 19).J. A. Burke, R. Levi, G. Zhao-gui and E.J. Corey. Leukotriene C4, D4 and E4: effects on human and guinea pig cardiac preparations in vitro. J. Pharmac. Exp. Ther. 235: 241, 1982.Google Scholar