Potassium Channel Openers, NIP-121 and Cromakalim, Enhance the Relaxation Induced by Sodium Nitroprusside in the Guinea-pig Isolated Trachea

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 microM indomethacin and then contracted with 30 nM leukotriene D4 (LTD4). Relaxant agents were added to the organ bath after the LTD4-elicited contraction had reached a plateau. 3. In epithelium-intact trachea, NIP-121 0.1 microM and cromakalim 1 microM, which did not modify the LTD4 (30 nM)-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 E2. 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 microM). 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.