Physiological consequences of beta-adrenoceptor desensitization in guinea pigs

The effects of repetitive doses of beta-adrenoceptor stimulants on the resting tone and responsiveness of bronchopulmonary smooth muscle were studied in guinea pigs. Collapse time was used to assess bronchospasm in conscious animals while resistance and compliance measurements were used in the anesthetized guinea pigs. Repetitive administration of either isoproterenol or salbutamol, at effective bronchodilator doses, caused an exacerbation of the histamine-induced bronchospasm in the presence or absence of anesthesia. Repetitive administration of either prostaglandin E1, 20 micrograms/kg i.m., or aminophylline, 400 micrograms/kg i.m. did not enhance histamine-induced bronchospasm. Furthermore, in guinea pigs preselected for lack of histamine sensitivity, treatment with salbutamol caused a decrease in both dynamic compliance values and peak expiratory flow rate as well as an increase in resistance values. Trachea removed from guinea pigs treated with isoproterenol or salbutamol retained normal responsiveness to histamine and dibutyryl cAMP while the responsiveness to isoproterenol was reduced. These studies indicate that repetitive administration of beta-adrenoceptor stimulants can produce a specific desensitization of beta-adrenoceptors in pulmonary tissue and an alteration of resting baseline values of pulmonary mechanics measurements.