Effects of furosemide and salbutamol on histamine- and methacholine-induced contraction of the isolated guinea-pig tracheal chain

The relaxant effect of furosemide on histamine- and methacholine-induced contraction was investigated in guinea-pig trachea in vitro with and without epithelial cells. The isolated tracheas of four to six guinea-pigs were used in each experiment and suspended in organ baths, filled with Krebs-Henseleit solution and aerated with 95% O-2 and 5% CO2. Furosemide (3 x 10(-5) M) produced a relaxation of 65.3 +/- 9.0% after histamine-induced contraction and 101.2 +/- 3.9% (3 x 10(-4) M) after methacholine-induced contraction compared to salbutamol (100%). At higher concentrations furosemide produced a relaxation of 74.8 x 2.5% after 10(-4) M furosemide for histamine-induced contraction and 110.4 +/- 5.3% (10(-3) M furosemide) for methacholine-induced contraction. Epithelial cell removal had no effect on the relaxant effect of furosemide for either agonist. Indomethacin pre-incubation (10(-6) M) also had no effect on the relaxant effect of furosemide for either agonist. These findings suggest that epithelial cells and their mediators are not involved in the relaxant effect of furosemide, and that the products of the cyclooxygenase pathway do not affect the smooth muscle relaxation caused by furosemide.