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 (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 β- 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 β2-adrenoceptor agonist-related processes.
|Journal||American Journal of Physiology - Lung Cellular and Molecular Physiology|
|Issue number||3 20-3|
|Publication status||Published - 1 Mar 1999|