Angiotensin II-mediated potentiation of endothelin-1-evoked bronchial contractions: a role for leukotrienes?
Angiotensin II potentiates the contractions evoked by endothelin-1. Previous studies have suggested that the mechanism underlying this effect may involve leukotrienes. The effects of the leukotriene synthesis inhibitor MK886 and of the leukotriene receptor antagonist ICI 198615 on angiotensin II-mediated potentiation of endothelin-1-induced contractions were examined. The ability of exogenously applied leukotriene D4 (3x10(-9)M) to potentiate the endothelin-1-induced contractions was also investigated. The presence of angiotensin II (3x10(-7)M) potentiated the constrictions evoked by endothelin-1 (e.g. 170% increase at 3x10(-7)M endothelin-1). In the presence of MK886 (10(-7)-10(-5)M), however, this potentiation was abolished. The presence of ICI 198615 (10(-7)-10(-5)M), likewise abolished the angiotensin II effect. The presence of leukotriene D4(3x10(-9)M), mimicked angiotensin II in significantly potentiating the endothelin-1-evoked responses. These data confirm previous work using nordihydroguaiaretic acid and suggest that leukotrienes contribute to the angiotensin II-mediated potentiation of endothelin-1-evoked contractions.
Pitt
C M
CM
School of Biological and Biomedical Sciences, Glasgow Caledonian University, 70 Cowcaddens Road, Glasgow, G4 0BA, UK.
Nally
J E
JE
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D019332:Endothelin-1 / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D017998:Leukotriene D4 / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D002722:Chlorobenzenes
D000804:Angiotensin II; D019332:Endothelin-1; D007191:Indazoles; D007211:Indoles; D020024:Leukotriene Antagonists; D017998:Leukotriene D4; D014662:Vasoconstrictor Agents; C060893:MK-886; D002722:Chlorobenzenes; C054217:ICI 198615