β2-Adrenoceptor agonists reduce the decline of rat diaphragm twitch force during severe hypoxia.

The aim of the present study was to investigate the in vitro effects of the short-acting β2-adrenoceptor agonist salbutamol and the long-acting β2-adrenoceptor agonist salmeterol on hypoxia-induced 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 [Formula: see text] 83.8 ± 0.9 kPa and [Formula: see text] 3.9 ± 0.1 kPa) or severe hypoxia ([Formula: see text] 7.1 ± 0.3 kPa and [Formula: see text] 3.9 ± 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-Poratio. Salmeterol treatment significantly reduced Po and increased the Pt-to-Poratio 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 β-adrenoceptor antagonist) did not alter Pt, Po, or the Pt-to-Poratio during hypoxia but completely blocked the inotropic effects of salbutamol and salmeterol, indicating that these effects are dependent on β2-adrenoceptor agonist-related processes.