Effects of salbutamol on rat diaphragm contractility.
The aim of this study was to investigate 1) the effects and time course of single doses of salbutamol on isometric contractile properties of isolated rat diaphragm strips and 2) whether these effects were caused by a direct effect on the muscle. Two experiments were performed. In one, salbutamol was administered subcutaneously in doses of 12.5, 25, 50, or 100 micrograms/kg (25 and 50 micrograms/kg sc resulted in serum concentrations of approximately 9 and approximately 15 micrograms/l, respectively, 0.5 h after injection) and in vitro contractile properties were determined 0.5, 1, 2, or 4 h after administration; in the other, salbutamol was added to the tissue bath in a concentration of < or = 2, approximately 10, approximately 20, and approximately 80 micrograms/l. Twice force, maximal tetanic force, and twitch force-to-tetanic force ratio all increased in a dose-dependent way in both experiments. The increases in force generation were slightly higher after subcutaneous administration. Force-frequency curves were shifted upward in both experiments. No significant effects of time of salbutamol administration were found, but the increase in force generation was most pronounced within 2 h after subcutaneous administration. In conclusion, in vitro force generation can be improved by low concentrations of salbutamol. The slightly higher increases in force generation after subcutaneous administration suggest that in vivo salbutamol may have additional positive inotropic actions on diaphragm contractility besides a direct beta 2-adrenergic effect on the muscle itself.
Van der Heijden
H F
HF
Department of Pulmonary Diseases, University Hospital Nijmegen, The Netherlands.
Van Balkom
R H
RH
Folgering
H T
HT
Van Herwaarden
C L
CL
Dekhuijzen
P N
PN
D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D003964:Diaphragm / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D000420:Albuterol