DIFFERENTIAL RELAXANT RESPONSES OF GUINEA-PIG LUNG STRIPS AND BRONCHIAL RINGS TO SODIUM-NITROPRUSSIDE - A MECHANISM INDEPENDENT OF CGMP FORMATION

The biochemical mechanism subserving smooth muscle relaxant effects of sodium nitroprusside was examined on U46619, 9,11-dideoxy-9 alpha,11 alpha-methanoepoxy PGF(2 alpha), precontracted guinea-pig lung strips and hilar bronchial rings. Lung strips were resistant to the relaxant action of sodium nitroprusside or sodium nitrite (NaNO2), whereas they markedly relaxed to 8-bromo-cyclic GMP (8-Br-cGMP), a membrane permea ble analogue of cGMP. Precontracted bronchial rings completely relaxed to sodium nitroprusside, NaNO2, or 8-Br-cGMP in a concentration-depen dent manner. Sodium nitroprusside (10 mu M) substantially raised tissu e cGMP level in lung strips. Conversely, sodium nitroprusside had no d etectable effect on cGMP levels in bronchial rings. In the presence of 10 mu M dipyridamole, an agent which preferentially inhibits cGMP-spe cific phosphodiesterase, cCMP levels in lung strips treated with sodiu m nitroprusside was significantly enhanced, but sodium nitroprusside d emonstrated no relaxant effect on the preparations. However, dipyridam ole potentiated sodium nitroprusside-induced precontracted bronchial r ing relaxation without affecting the bronchial tissue cGMP level. In t he presence of 10 mu M LY83583 (6-anilino-5,8-quinoline-dione), a spec ific cGMP concentration-lowering agent, sodium nitroprusside-mediated elevation of cGMP level in lung strips was significantly reduced with no effect on the functional response. LY83583 demonstrated no inhibito ry effect on either relaxation or cGMP level in bronchial rings treate d with sodium nitroprusside. Our results suggest that precontracted sm ooth muscle in lung strips and in hilar bronchi respond distinctly to sodium nitroprusside. Furthermore, sodium nitroprusside mediates bronc hial smooth muscle relaxation by mechanisms unrelated to cGMP.