K-DEPENDENT RELAXATION OF THE GUINEA-PIG TRACHEA( CHANNEL OPENERS PRODUCE EPITHELIUM)

The relaxant effects of the K+ channel openers, NIP-121, idin-1-yl)-6H -pyranol[2,3-f]benz-2,1,3-oxadiazole, and cromakalim, were investigate d in epithelium-intact and -denuded tracheal spirals isolated from gui nea-pigs. In the presence of 5 mu M indomethacin, NIP-121 (0.01-1 mu M ) and cromakalim (0.1-10 mu M) relaxed, in a concentration-dependent m anner, epithelium-intact and -denuded trachea precontracted with a thr omboxane A(2) mimetic, U46619, 9,11-dideoxy-9 alpha,11 alpha-methanoep oxy-prostaglandin F-2 alpha (30 nM). The relaxations of epithelium-den uded trachea were significantly decreased as compared with those of ep ithelium-intact trachea. The relaxations induced by salbutamol or amin ophylline were not affected by epithelium removal. In epithelium-intac t trachea, the NIP-121- and cromakalim-induced relaxations were not mo dulated by the neutral endopeptidase inhibitor, phosphoramidon (10 mu M), or the nitric oxide synthesis inhibitor, N-omega-nitro-L-arginine (100 mu M). However, the guanylate cyclase inhibitor, methylene blue ( 100 mu M), significantly reduced NIP-121- and cromakalim-induced relax ation of epithelium-intact trachea. Methylene blue also reduced sodium nitroprusside-induced relaxation but did not affect isoprenaline-indu ced relaxation. These findings suggest that the K+ channel openers, NI P-121 and cromakalim, may induce, at least in part, epithelium-depende nt and methylene blue-sensitive relaxation of the guinea-pig isolated trachea.