The aim of the present study was to investigate the in vitro effects of the short-acting ₂-adrenoceptor agonist salbutamol and the long-acting ₂-adrenoceptor agonist salmeterol on hypoxia-induced rat diaphragm force reduction. In vitro diaphragm twitch force (P_t) and maximal tetanic force (P_o) of isolated diaphragm muscle strips were measured for 90 min during 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 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 P_t and P_o (to ~50% of initial values). Salbutamol had no effects on P_o or the P_t-to-P_o ratio. Salmeterol treatment significantly 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 ~30% of initial value) and P_o after 90 min. Both salbutamol 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 longer duration of action. Addition of 1 µM propranolol (a nonselective -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 and salmeterol, indicating that these effects are dependent on ₂-adrenoceptor agonist-related processes.

contractile properties; respiratory muscles; salmeterol; salbutamol

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