FUROSEMIDE-INDUCED BRONCHODILATION IN THE RAT BRONCHUS - EVIDENCE OF A ROLE FOR PROSTAGLANDINS

Pretreatment with inhaled fuorsemide has been shown to protect against bronchoconstrictive stimuli that indirectly activate airway smooth mu scle. However, it is controversial as to whether furosemide acts direc tly on airway smooth muscle. To investigate this we studied the effect of furosemide on both methacholine (MCh)- and serotonin (5-HT)-induce d bronchoconstriction in explanted rat airways. Lungs from 21 Sprague- Dawley rats (269 +/- 15 g) were excised, inflated with agarose solutio n at 37 degrees C (1% w/v, 48 ml/kg), embedded in 4% agarose, and refr igerated to gel the agarose. Lung slices (0.5-1.0 mm thick) were cultu red overnight at 37 degrees C. Explants were placed on a dissecting vi deo microscope, and airway area was measured with an image analysis sy stem. MCh or 5-HT was administered directly to explanted airways (fina l concentrations 3.8 x 10(-6) M and 3.8 x 10(-5) M, respectively). Fiv e min later furosemide (3.7 x 10(-5) M or 3.7 x 10(-4) M) was added an d airway area monitored 5, 10, 15, 30, and 60 min later. Results were expressed as a percentage of the maximal response. Significant broncho dilation was seen after 30 min in airways preconstricted with MCh and after 15 min in those preconstricted with 5-HT following 3.7 x 10(-4) M furosemide (p < 0.05). 3.7 x 10(-5) M furosemide caused bronchodilat ion only at 60 min in airways constricted with 5-HT. The effect was bl ocked by a 30-min incubation of explants with 10(-6) M indomethacin. T he furosemide-induced bronchodilation effect was not observed in airwa ys strongly constricted with 3.8 x 10(-5) M MCh. These findings indica te that in the rat at least, furosemide induces a weak bronchodilator effect present only at high doses, which seems to be dependent on the production of prostaglandins. This effect may be relevant to the obser ved therapeutic action of furosemide in asthmatics.