Disodium cromoglycate does not prevent terbutaline-induced desensitizationof beta(2)-adrenoceptor-mediated cardiovascular in vivo functions in humanvolunteers

In humans, prolonged administration of the beta(2)-andrenoceptor agonist te rbutaline leads to a desensitization of beta(2)-adrenoceptor-mediated cardi ovascular responses, which can be blunted by concomitant administration of the antianaphylactic drug ketotifen. This study investigated the effect of disodium cromoglycate, another antiallergic drug, on terbutaline-induced de sensitization of beta-adrenoceptor-mediated cardiovascular and noncardiovas cular responses. In a double-blind, placebo-controlled, randomized design, nine healthy male volunteers received disodium cromoglycate (4 x 200 mg/day , p.o.) or placebo for 3 weeks with terbutaline (3 x 5 mg/day, p.o.) admini stered concomitantly during the last 2 weeks. beta(2)-Adrenoceptor cardiova scular function was assessed by the increase in heart rate and reduction of diastolic blood pressure induced by an incremental intravenous infusion of the unselective beta-adrenoceptor agonist isoprenaline; beta(1)-adrenocept or cardiovascular function was assessed by exercise-induced tachycardia. Tr emulousness was monitored as a beta(2)-adrenoceptor-mediated noncardiovascu lar effect. After 2 weeks' administration of terbutaline. there was a marke d and significant (p < 0.001) attenuation of isoprenaline-induced tachycard ia (mean percentage attenuation, 53.3%) and of the isoprenaline-induced dec rease in diastolic blood pressure (mean percentage attenuation, 55.6%). Exe rcise-induced tachycardia also was significantly (p < 0.001) blunted, but t he magnitude of this attenuation was only very small (mean attenuation, 5.6 %). Disodium cromoglycate affected neither the rightward shift of beta(2)-a drenoceptor-mediated responses nor the small rightward shift in beta(1)-adr enoceptor-mediated exercise tachycardia after 2 weeks' administration of te rbutaline. Tremulousness observed during the first few days of terbutaline administration disappeared after 4 to 8 days, indicating development of des ensitization of beta(2)-adrenoceptor-mediated noncardiovascular responses. This was not prevented by disodium cromoglycate. These results confirm that long-term beta(2)-adrenoceptor agonist therapy leads to a desensitization of beta(2)-adrenoceptor-mediated cardiovascular and noncardiovascular effec ts in humans in vivo. However, unlike ketotifen, cromolyn sodium is not abl e to attenuate this desensitization.