beta(2)-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 beta(2)-adrenoceptor agonist salbutamol and the long-acting b eta(2)-adrenoceptor agonist salmeterol on hypoxia-induced rat diaphragm for ce reduction. In vitro diaphragm twitch force (P-t) and maximal tetanic for ce (P-o) of isolated diaphragm muscle strips were measured for 90 min durin g hyperoxia (tissue bath PO2 83.8 +/- 0.9 kPa and PCO2 3.9 +/- 0.1 kPa) or severe hypoxia (PO2 7.1 +/- 0.3 kPa and PCO2 3.9 +/- 0.1 kPa) in the presen ce and absence of 1 mu M salbutamol or 1 mu M salmeterol. During hyperoxia, salbutamol and salmeterol did not significantly alter the time-related dec reases in P-t and P-o (to similar to 50% of initial values). Salbutamol had no effects on P-o or the P-t-to-P-o ratio. Salmeterol treatment significan tly reduced P-o and increased the P-t-to-P-o ratio during hyperoxia (P < 0. 05 compared with control value). Hypoxia resulted in a severe decrease in P -t (to similar to 30% of initial value) and P-o after 90 min. Both salbutam ol and salmeterol significantly reduced the decline in P-t during hypoxia ( P < 0.05). The reduction in P-o was not prevented. Salbutamol increased P-t rapidly but transiently. Salmeterol had a delayed onset of effect and a lo nger duration of action. Addition of 1 mu M propranolol (a nonselective bet a-adrenoceptor antagonist) did not alter P-t, P-o, or the P-t-to-P-o ratio during hypoxia but completely blocked the inotropic effects of salbutamol a nd salmeterol, indicating that these effects are dependent on beta(2)-adren oceptor agonist-related processes.