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• W2081432983 abstract "1 Using an X-ray microangiographic technique in rabbit isolated perfused ears preconstricted with 5-HT (300 nm) and histamine (300 nm), we investigated the combined actions of Nω-nitro-l-arginine methyl ester (l-NAME) and indomethacin on acetylcholine-induced depressor responses. 2 Under control conditions, acetylcholine (10 nm–30 μm) induced a concentration-dependent reversal of the pressor response, reaching a maximum of 66.0±13.6% (n = 6). In the presence of l-NAME (300 μm) and indomethacin (10 μm), this depressor action was reduced, reaching a maximum of 38.6±5.9% (n = 6). 3 The control response was associated with substantial vasodilatation in the central ear artery (G0), a smaller dilatory action on first generation branch arteries (G1) and no effect on second generation branch arteries (G2). In the presence of l-NAME and indomethacin, vasodilatation occurred in G2 with no effect in G0 or G1. 4 Two calcium-activated K+ channels blockers, charybdotoxin (ChTX; 10 nm) and penitrem A (100 nm), further inhibited, but did not abolish, the l-NAME- and indomethacin-resistant response to acetylcholine (10 nm–300 μm). Both agents abolished the vasodilatory action of acetylcholine in G2. 5 In conclusion, l-NAME and indomethacin induced a shift in acetylcholine-induced vasodilatation from G0 and G1 to G2. This is consistent with the suggestion that nitric oxide dominates in larger vessels whilst other mechanisms dominate in smaller vessels. The l-NAME- and indomethacin-resistant component was inhibited by ChTX and penitrem A, suggesting it is mediated, at least in part, by activation of KCa channels and could therefore involve a hyperpolarising mediator such as endothelium-derived hyperpolarising factor. British Journal of Pharmacology (1998) 124, 1245–1253; doi:10.1038/sj.bjp.0701945" @default.
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• W2081432983 title "Spatial heterogeneity in the mechanisms contributing to acetylcholine-induced dilatation in the rabbit isolated ear" @default.
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• W2081432983 doi "https://doi.org/10.1038/sj.bjp.0701945" @default.
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