CHARACTERIZATION OF TOLERANCE TO THE ANTI-LEAKAGE EFFECT OF FORMOTEROL IN RAT AIRWAYS

These experiments addressed the question of whether the anti-plasma le akage action of beta(2)-adrenoceptor agonists in rat airways is subjec t to tolerance. Pathogen-free F344 rats were pretreated with the highl y selective, long-acting beta(2)-adrenoceptor agonist, formoterol (0, 0.1, 1, 10 mu g/kg, i.p.) for 7 days; 24 h later the effectiveness of acute doses of formoterol (0, 0.1, 1, 10 mu g/kg, i.v.) was tested aga inst substance P-induced plasma leakage. The anti-leakage effect of fo rmoterol was not subject to tolerance with the low or intermediate pre treatment dose. Pretreatment with 10 mu g/kg formoterol reduced the ef fectiveness of the 1 mu g/kg acute dose but not the 10 mu g/kg acute d ose. We conclude that tolerance to the anti-leakage effect of formoter ol carl occur, but airway vessels are likely to retain functionally co upled receptors even after high dose pretreatment. (C) 1997 Elsevier S cience B.V.