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Potassium channel openers, NIP‐121 and cromakalim, enhance the relaxation induced by sodium nitroprusside in the guinea‐pig isolated trachea
Author(s) -
Shikada Kenichi,
Tanaka Sakuya
Publication year - 1992
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 - 10.1111/j.1476-5381.1992.tb13416.x
Subject(s) - cromakalim , pinacidil , sodium nitroprusside , potassium channel , potassium channel opener , chemistry , guinea pig , potassium , sodium , sodium channel , pharmacology , medicine , endocrinology , biochemistry , agonist , nitric oxide , receptor , glibenclamide , organic chemistry , diabetes mellitus
1 The effect of the potassium channel openers, NIP‐121 and cromakalim, on agonist‐induced relaxation of the guinea‐pig isolated trachea was investigated and the results were compared with those in the epithelium‐denuded trachea. 2 Tracheal strips were incubated with a potassium channel opener or vehicle for 30 min in the presence of 5 μ m indomethacin and then contracted with 30 n m leukotriene D 4 (LTD 4 ). Relaxant agents were added to the organ bath after the LTD 4 ‐elicited contraction had reached a plateau. 3 In epithelium‐intact trachea, NIP‐121 0.1 μ m and cromakalim 1 μ m , which did not modify the LTD 4 (30 n m )‐induced contraction, significantly enhanced the sodium nitroprusside (SNP)‐induced relaxation. This enhancement of relaxation was not seen in the case of relaxation induced by the cyclic AMP‐dependent bronchodilators isoprenaline, vasoactive intestinal peptide or prostaglandin E 2 . The enhancement of SNP‐induced relaxation by NIP‐121 and cromakalim was abolished in the presence of the ATP‐sensitive potassium channel blocker, glibenclamide (1 μ m ). NIP‐121 and cromakalim did not produce any significant changes in the relaxation induced by 8‐bromoguanosine‐cyclic monophosphate (8‐Br‐cyclic GMP), a cyclic GMP analogue. 4 In epithelium‐denuded trachea, SNP‐induced relaxation alone was significantly enhanced but that induced by 8‐Br‐cyclic GMP was not changed. Neither NIP‐121 nor cromakalim enhanced SNP‐induced relaxation in denuded trachea. 5 These results suggest that in the presence of an intact epithelium the enhancement by NIP‐121 and cromakalim of the relaxation of guinea‐pig tracheal smooth muscle induced by SNP may be associated with the opening of glibenclamide‐sensitive potassium channels.