Abstract
These experiments addressed the question of whether the anti-plasma leakage action of β 2-adrenoceptor agonists in rat airways is subject to tolerance. Pathogen-free F344 rats were pretreated with the highly selective, long-acting β 2-adrenoceptor agonist, formoterol (0, 0.1, 1, 10 μg/kg, i.p.) for 7 days; 24 h later the effectiveness of acute doses of formoterol (0, 0.1, 1, 10 μg/kg, i.v.) was tested against substance P-induced plasma leakage. The anti-leakage effect of formoterol was not subject to tolerance with the low or intermediate pretreatment dose. Pretreatment with 10 μg/kg formoterol reduced the effectiveness of the 1 μg/kg acute dose but not the 10 μg/kg acute dose. We conclude that tolerance to the anti-leakage effect of formoterol can occur, but airway vessels are likely to retain functionally coupled receptors even after high dose pretreatment.
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