b2-Adrenoceptor agonists reduce the decline of rat diaphragm twitch force during severe hypoxia

Van der Heijden, H. F. M., L. M. A. Heunks, H. Folgering, C. L. A. van Herwaarden, and P. N. R. Dekhuijzen. b2-Adrenoceptor agonists reduce the decline of rat diaphragm twitch force during severe hypoxia. Am. J. Physiol. 276 (Lung Cell. Mol. Physiol. 20): L474–L480, 1999.—The aim of the present study was to investigate the in vitro effects of the short-acting b2-adrenoceptor agonist salbutamol and the long-acting b2-adrenoceptor agonist salmeterol on hypoxiainduced rat diaphragm force reduction. In vitro diaphragm twitch force (Pt) and maximal tetanic force (Po) of isolated diaphragm muscle strips were measured for 90 min during hyperoxia (tissue bath PO2 83.8 6 0.9 kPa and PCO2 3.9 6 0.1 kPa) or severe hypoxia (PO2 7.1 6 0.3 kPa and PCO2 3.9 6 0.1 kPa) in the presence and absence of 1 μM salbutamol or 1 μM salmeterol. During hyperoxia, salbutamol and salmeterol did not significantly alter the time-related decreases in Pt and Po (to ,50% of initial values). Salbutamol had no effects on Po or the Pt-to-Po ratio. Salmeterol treatment significantly reduced Po and increased the Pt-to-Po ratio during hyperoxia (P , 0.05 compared with control value). Hypoxia resulted in a severe decrease in Pt (to ,30% of initial value) and Po after 90 min. Both salbutamol and salmeterol significantly reduced the decline in Pt during hypoxia (P , 0.05). The reduction in Po was not prevented. Salbutamol increased Pt rapidly but transiently. Salmeterol had a delayed onset of effect and a longer duration of action. Addition of 1 μM propranolol (a nonselective b-adrenoceptor antagonist) did not alter Pt, Po, or the Pt-to-Po ratio during hypoxia but completely blocked the inotropic effects of salbutamol and salmeterol, indicating that these effects are dependent on b2-adrenoceptor agonistrelated processes.