INFLUENCE OF CHRONIC HYPOXIA ON SALBUTAMOL TISSULAR CONCENTRATIONS AND ON RESPIRATORY RESISTANCE IN ANESTHETIZED RABBITS

Salbutamol is a potent beta(2)-adrenoceptor agonist given to patients with bronchial asthma who are frequently hypoxemic. The aims of this s tudy were to document the influence of chronic hypoxia on salbutamol t issue concentrations and on salbutamol effect on total respiratory res istance. To this purpose, salbutamol (60 mu g/kg) was administered int ravenously to four groups of six rabbits exposed to four experimental conditions: (1) control rabbits breathing air, (2) histamine-induced b ronchoconstriction in rabbits breathing air, (3) animals with chronic hypoxia, (4) histamine-induced bronchoconstriction in animals with chr onic hypoxia. The area under salbutamol plasma concentration time curv e (0 to 45 min) was not affected by these experimental conditions. Com pared with control rabbits breathing air, following histamine-induced bronchoconstriction, salbutamol concentrations rose by 40 to 50% in lu ng and heart (p < 0.05). Hypoxia did not affect salbutamol distributio n in these organs; however, in hypoxic animals, histamine-induced bron choconstriction 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 eff ect of salbutamol was reduced in rabbits under chronic hypoxia and his tamine-induced bronchoconstriction (p < 0.05). We conclude that chroni c hypoxia reduces salbutamol effect on pulmonary resistance, possibly by decreasing salbutamol lung concentrations.