Sex Hormones Modulate Salbutamol-Elicited Long-Term Relaxation in Isolated Bovine Tracheal Strips

Abstract

Sex hormones are of interest regarding gender differences in the clinical manifestations of airway diseases. No conclusive data are available on the sex hormone modulation of β-adrenoceptor-mediated responses on airways. To this aim, isolated preparations of bovine trachea were used to establish the sex hormone influence on salbutamol-elicited relaxation. This had 2 components, a full acute relaxation followed by a loss of efficacy, close to half of the effect. The remaining half was reverted by the β-blocker, propranolol. The loss of salbutamol-elicited relaxation might reflect the receptor desensitization, as shown by the lack of effect by subsequent administration of salbutamol, and the decrease in the immunostaining of β₂-adrenoceptors. Sex hormones differently modified the salbutamol-elicited response. Testosterone, but not other androgens or estradiol, had a synergic effect, facilitating the acute relaxation and decreasing the loss of spasmolytic effect, associated with an increase in the latency of desensitization and a decrease in the time taken to reach long-term steady-state tone. These effects, not modified by the antiandrogen flutamide or epithelium removal, seem to be independent of a modulation of β₂-adrenoceptor desensitization. Testosterone also relaxed preparations with desensitized β-adrenoceptor. Therefore, testosterone modulates tracheal smooth muscle tone, facilitating bronchodilation caused by β₂-adrenoceptor agonists which might be of pharmacological interest.