S Perreault, C Saunier, C Duvivier, R Peslin, H Ong and P Du Souich
Department of Pharmacology, Faculty of Medicine, University of Montreal, Quebec, Canada.

Salbutamol is a potent beta 2-adrenoceptor agonist given to patients with bronchial asthma who are frequently hypoxemic. The aims of this study were to document the influence of chronic hypoxia on salbutamol tissue concentrations and on salbutamol effect on total respiratory resistance. To this purpose, salbutamol (60 micrograms/kg) was administered intravenously to four groups of six rabbits exposed to four experimental conditions: (1) control rabbits breathing air, (2) histamine-induced bronchoconstriction in rabbits breathing air, (3) animals with chronic hypoxia, (4) histamine-induced bronchoconstriction in animals with chronic hypoxia. The area under salbutamol plasma concentration time curve (0 to 45 min) was not affected by these experimental conditions. Compared with control rabbits breathing air, following histamine-induced bronchoconstriction, salbutamol concentrations rose by 40 to 50% in lung and heart (p < 0.05). Hypoxia did not affect salbutamol distribution in these organs; however, in hypoxic animals, histamine-induced bronchoconstriction increased salbutamol concentrations only in the heart (p < 0.05), without affecting those in the lung. Compared with rabbits breathing air and with histamine-induced bronchoconstriction, the effect of salbutamol was reduced in rabbits under chronic hypoxia and histamine-induced bronchoconstriction (p < 0.05). We conclude that chronic hypoxia reduces salbutamol effect on pulmonary resistance, possibly by decreasing salbutamol lung concentrations.