The Role of Cyclooxygenase and 5-Lipoxygenase Metabolites in Potentiated Endothelin-1-evoked Contractions in Bovine Bronchi
✍ Scribed by Jane E. Nally; David C. Bunton; David Martin; Neil C. Thomson
- Publisher
- Elsevier
- Year
- 1996
- Tongue
- English
- Weight
- 258 KB
- Volume
- 9
- Category
- Article
- ISSN
- 0952-0600
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✦ Synopsis
We have previously shown that angiotensin II (AII) potentiates responses evoked by endothelin-1 (Et-1). In the present study, the additional ability of hypoxia or phorbol 12, 13-dibutyrate (PDBu) to evoke hyperreactivity was examined. In addition, the role of cyclooxygenase and 5-lipoxygenase metabolites of arachidonic acid in the potentiation evoked by AII, hypoxia or PDBu was studied, using indomethacin and nordihydroguaiaretic acid (NDGA). The involvement of protein kinase C in the enhanced response was examined using staurosporine. Contractions were measured isometrically from rings of bovine bronchi. Contractions evoked by Et-1 alone were unaltered by indomethacin (10(-6)M), NDGA (10(-5)M) or staurosporine (3 x 10(-8)M). AII (3 x 10(-7)M), hypoxia (4% O2) or PDBu (10(-8)M) each significantly potentiated the contractions evoked by Et-1. Indomethacin (10(-6)M) virtually abolished the effect of AII, hypoxia or PDBu. NDGA (10(-5)M) reversed the potentiating effect of both AII and hypoxia and partially reversed PDBu-evoked enhancement of Et-1-mediated responses. Staurosporine (3 x 10(-8)M) abolished the ability of AII or PDBu, but not hypoxia, to enhance Et-1-mediated contractions. In conclusion, AII, hypoxia and PDBu evoke hyperresponsiveness which is mediated by prostanoids and/or leukotrienes, the precise nature of which remains to be elucidated. Differences in the ability of staurosporine to reverse AII- and hypoxia-induced hyperreactivity suggests, however, that these conditions may generate different eicosanoids.