Inotropic effects of salbutamol on rat diaphragm contractility are potentiated by foreshortening.

The aim of this study was to investigate whether the positive inotropic effects of the beta 2-adrenoceptor agonist salbutamol are increased by foreshortening of the diaphragm, and to determine the mechanism of action of these effects. Diaphragm strips were studied either at optimal resting length (Lo) or at approximately 70% Lo. In an initial experiment (Experiment I) salbutamol was added to the tissue baths in concentrations of 10 micrograms/L or 80 micrograms/L. In a second experiment (Experiment II), the effect of salbutamol (80 micrograms/L) was measured in the presence of 1 microM ryanodine, a sarcoplasmatic reticulum (SR) Ca(2+)-release inhibitor. Each experiment had a time-matched control group. Foreshortening reduced twitch force (Pt), maximal tetanic force (Po), and force-frequency curves. Salbutamol increased Pt and Po both at Lo and approximately 70% Lo. These inotropic effects were significantly greater after foreshortening. The force-frequency curve was shifted upward by salbutamol at both lengths. Force-frequency curves relative to maximal percent of Po were depressed by salbutamol at stimulation frequencies of 80 to 160 Hz. Ryanodine blocked the inotropic effect of salbutamol at both muscle lengths, indicating that these inotropic effects are probably mediated by increased SR Ca2+ release.