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.
Shikada
K
K
Shiraoka Research Station of Biological Science, Nissan Chemical Industries Ltd., Saitama, Japan.
Tanaka
S
S
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004347:Drug Interactions; D004848:Epithelium / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D013189:SRS-A / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D010069:Oxadiazoles; D010880:Piperidines; D015221:Potassium Channels; D011758:Pyrroles; D013189:SRS-A; D014665:Vasodilator Agents; D019806:Cromakalim; D009599:Nitroprusside; C016276:8-bromocyclic GMP; C070366:NIP 121; D006152:Cyclic GMP