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• W2084570265 abstract "1 To clarify further the role of cyclic GMP in mediating the relaxant response in guinea-pig trachea induced by sodium nitroprusside (SNP), the effects of soluble guanylyl cyclase inhibitors, methylene blue and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) on SNP-induced muscle relaxation and cyclic GMP accumulation were determined. 2 SNP (0.3–100 μm) evoked a concentration-dependent relaxation of guinea-pig isolated tracheas precontracted with 0.3 μm carbachol. Preincubation of the preparations with methylene blue (10, 30 and 100 μm) resulted in a slight but concentration-dependent prevention of the relaxant response to SNP. In contrast, the relaxation to SNP was extensively prevented by 3 μm ODQ and almost abolished by 10 μm ODQ. 3 SNP (30 μm) induced a significant elevation of cyclic GMP accumulation (from 1.34±0.14 to 5.39±0.28 pmol mg−1 protein, n = 5; P < 0.001), which was partially attenuated by 100 μm methylene blue (3.11±0.51 pmol mg−1 protein, n = 5; P < 0.05), whereas completely abolished by 10 μm ODQ (1.31±0.28 pmol mg−1 protein, n = 5; P < 0.001). 4 Methylene blue, but not ODQ and Nω-nitro-l-arginine methyl ester (l-NAME), caused a concentration-dependent contraction in the tracheal preparation. The tension produced by 100 μm methylene blue was 41.8±4.3% (0.3 μm carbachol as 100%; n=12). Moreover, the non-selective muscarinic receptor antagonist atropine and the M3-selective antagonist 4-diphenylacetoxy-N-methylpiperidine methiodine greatly inhibited the contractile effect evoked by methylene blue (100 μm). 5 In conclusion, this study provides substantial evidence that SNP-induced muscle relaxation in guinea-pig trachea is completely via a cyclic GMP-dependent mechanism. Furthermore, ODQ, but not methylene blue, will likely become an important tool in differentiating between cyclic GMP-dependent and -independent effects of nitric oxide. British Journal of Pharmacology (1998) 125, 1158–1163; doi:10.1038/sj.bjp.0702181" @default.
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• W2084570265 date "1998-11-01" @default.
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• W2084570265 title "Comparison of two soluble guanylyl cyclase inhibitors, methylene blue and ODQ, on sodium nitroprusside-induced relaxation in guinea-pig trachea" @default.
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• W2084570265 doi "https://doi.org/10.1038/sj.bjp.0702181" @default.
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