Am. J. Respir. Crit. Care Med., Vol 155, No. 3, Mar 1997, 1072-1079.
Inotropic effects of salbutamol on rat diaphragm contractility are potentiated by foreshortening
HF van der Heijden, PN Dekhuijzen, H Folgering and CL van Herwaarden
Department of Pulmonary Diseases, University Hospital Nijmegen, The Netherlands.
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.
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Copyright © 1997 American Thoracic Society
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