K+ channel openers produce epithelium-dependent relaxation of the guinea-pig trachea.
The relaxant effects of the K+ channel openers, NIP-121, (+)-7,8-dihydro-6,6-dimethyl-7-hydroxy-8-(2-oxo-piperidin-1-yl)-6H - pyrano[2,3-f]benz-2,1,3-oxadiazole, and cromakalim, were investigated in epithelium-intact and -denuded tracheal spirals isolated from guinea-pigs. In the presence of 5 microM indomethacin, NIP-121 (0.01-1 microM) and cromakalim (0.1-10 microM) relaxed, in a concentration-dependent manner, epithelium-intact and -denuded trachea precontracted with a thromboxane A2 mimetic, U46619, 9,11-dideoxy-9 alpha, 11 alpha-methanoepoxy-prostaglandin F2 alpha (30 nM). The relaxations of epithelium-denuded trachea were significantly decreased as compared with those of epithelium-intact trachea. The relaxations induced by salbutamol or aminophylline were not affected by epithelium removal. In epithelium-intact trachea, the NIP-121- and cromakalim-induced relaxations were not modulated by the neutral endopeptidase inhibitor, phosphoramidon (10 microM), or the nitric oxide synthesis inhibitor, N omega-nitro-L-arginine (100 microM). However, the guanylate cyclase inhibitor, methylene blue (100 microM), significantly reduced NIP-121- and cromakalim-induced relaxation of epithelium-intact trachea. Methylene blue also reduced sodium nitroprusside-induced relaxation but did not affect isoprenaline-induced relaxation. These findings suggest that the K+ channel openers, NIP-121 and cromakalim, may induce, at least in part, epithelium-dependent and methylene blue-sensitive relaxation of the guinea-pig isolated trachea.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D004848:Epithelium / Q000187:drug effects; D006168:Guinea Pigs; D008297:Male; D008751:Methylene Blue; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D010069:Oxadiazoles / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D015221:Potassium Channels / Q000819:agonists*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D001578:Benzopyrans; D010069:Oxadiazoles; D010880:Piperidines; D015221:Potassium Channels; D011450:Prostaglandin Endoperoxides, Synthetic; D011758:Pyrroles; D019806:Cromakalim; D019335:Nitroarginine; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C070366:NIP 121; D001120:Arginine; D019001:Nitric Oxide Synthase; D008751:Methylene Blue