Characterization of tolerance to the anti-leakage effect of formoterol in rat airways.
These experiments addressed the question of whether the anti-plasma leakage action of beta2-adrenoceptor agonists in rat airways is subject to tolerance. Pathogen-free F344 rats were pretreated with the highly selective, long-acting beta2-adrenoceptor agonist, formoterol (0, 0.1, 1, 10 microg/kg, i.p.) for 7 days; 24 h later the effectiveness of acute doses of formoterol (0, 0.1, 1, 10 microg/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 microg/kg formoterol reduced the effectiveness of the 1 microg/kg acute dose but not the 10 microg/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.
Bowden
J J
JJ
Cardiovascular Research Institute and Department of Anatomy, University of California, San Francisco 94143-0130, USA.
Anderson
G P
GP
Lefevre
P M
PM
Sulakvelidze
I
I
McDonald
D M
DM
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004361:Drug Tolerance; D004983:Ethanolamines / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013373:Substance P / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D013373:Substance P; D000068759:Formoterol Fumarate