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Comparison of two soluble guanylyl cyclase inhibitors, methylene blue and ODQ, on sodium nitroprusside‐induced relaxation in guinea‐pig trachea
Author(s) -
Hwang TsongLong,
Wu ChinChung,
Teng CheMing
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702181
Subject(s) - soluble guanylyl cyclase , sodium nitroprusside , carbachol , methylene blue , chemistry , guinea pig , muscarinic acetylcholine receptor , endocrinology , nitric oxide , medicine , antagonist , snap , biochemistry , receptor , biology , guanylate cyclase , computer graphics (images) , photocatalysis , computer science , catalysis
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 μ m ) evoked a concentration‐dependent relaxation of guinea‐pig isolated tracheas precontracted with 0.3 μ m carbachol. Preincubation of the preparations with methylene blue (10, 30 and 100 μ m ) 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 μ m ODQ and almost abolished by 10 μ m ODQ. 3 SNP (30 μ m ) 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 μ m methylene blue (3.11±0.51 pmol mg −1 protein, n = 5 ; P < 0.05 ), whereas completely abolished by 10 μ m ODQ (1.31±0.28 pmol mg −1 protein, n = 5 ; P < 0.001 ). 4 Methylene blue, but not ODQ and N ω ‐nitro‐ l ‐arginine methyl ester ( l ‐NAME), caused a concentration‐dependent contraction in the tracheal preparation. The tension produced by 100 μ m methylene blue was 41.8±4.3% (0.3 μ m carbachol as 100%; n =12). Moreover, the non‐selective muscarinic receptor antagonist atropine and the M 3 ‐selective antagonist 4‐diphenylacetoxy‐N‐methylpiperidine methiodine greatly inhibited the contractile effect evoked by methylene blue (100 μ m ). 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