Salbutamol-induced airway hyperreactivity in guinea pigs is not due to a loss of its bronchodilator effect.
Guinea pigs were treated for 10 days with (+/-)-salbutamol (0.2 mg/kg/day, delivered from subcutaneously implanted osmotic minipumps). Airway reactivity to intravenously administered histamine, methacholine and bombesin was substantially increased in salbutamol-treated guinea pigs relative to controls. In the same animals, the potency of intravenously administered salbutamol to reverse bombesin-induced bronchoconstriction remained unchanged thus exactly reflecting effects in man. In conclusion, subchronic administration of salbutamol at low doses to guinea pigs increases airway reactivity. Since the bronchorelaxant effect of salbutamol remained unchanged, desensitisation of beta-adrenoceptors on airway smooth muscle is unlikely to account for this effect.
Buchheit
K H
KH
Preclinical Research, Sandoz Pharma Ltd., Basel, Switzerland.
Hofmann
A
A
Fozard
J R
JR
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000420:Albuterol / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001839:Bombesin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced*; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D018377:Neurotransmitter Agents; D016210:Methacholine Chloride; D006632:Histamine; D001839:Bombesin; D000420:Albuterol