The effects of chronic inhalation of salbutamol on the acute airway responsiveness to salbutamol and ipratropium bromide in the conscious and the anaesthetized guinea-pig

Abstract

Abstract The effects of chronic exposure to a nebulized mist of salbutamol on the capacity of systemic salbutamol to prolong the time taken for inhaled histamine to produce bronchospasm in guinea-pigs have been examined. Initially a reproducible cough time to inhalation of histamine acid phosphate (0·5 ml ml−1) in 100% O2 was established. Antagonism of this response by intraperitoneal salbutamol or ipratropium Br was assessed to establish submaximal responses to these drugs. A fresh group of animals was then exposed to a persistent mist of nebulized water for 16 days, before and during which each animal was tested by exposure to histamine mist either alone or shortly after salbutamol (10 μg kg−1 i.p.) or ipratropium Br (5 μg kg−1 i.p.). The nebulized water had no effect on the response to the drugs. The same animals were rested for 7 days and then exposed to nebulized salbutamol solution (5 mg ml−1) for 15 days, during which time tachyphylaxis developed to salbutamol (i.p.) but not to ipratropium Br. At the end of the 15 days the animals were anaesthetized and total lung resistance (RL) measured. At this time, the protective effect of intravenous salbutamol was also diminished by comparison with untreated guinea-pigs while the response to ipratropium Br was unaffected. A separate group exposed to 1 mg ml−1 of nebulized salbutamol for 20 days developed selective tachyphylaxis to intraperitoneal salbutamol. The animals were then allowed to breathe room air and the reponse to intraperitoneal salbutamol after 13 days returned to normal as did the effects of intravenous salbutamol on the RL response to histamine.