Rat skeletal muscle contractility: The role of beta-adrenoceptors and nitric oxide system

Abstract

Both beta-adrenoceptors and the nitric oxide system play a significant role in the modulation of skeletal muscle contractility. Skeletal muscle adrenoceptors mainly belong to beta2 subtype, while all three types of nitric oxide synthase may influence muscle contractility. The aim of our study was to investigate the possible interplay between beta-adrenoceptor agonists and nitric oxide system in the modulation of contractility of isolated rat hemidiaphragm. Adrenaline (0.05-1.5 μmol/L) and noradrenaline (1-5 μmol/L) given in a cumulative manner produced a concentration-related increase in Td. L-NAME (1, 3 and 10 mmol/L; 30 min of incubation) produced a significant, dose-dependent increase in Td of the muscle pretreated with cumulative concentrations of adrenaline (ΔTd up to 16%). When hemidiaphragm was pretreated with noradrenaline instead of adrenaline, L-NAME (3 mmol/L) it produced a similar potentiation of Td. In conclusion, nitric oxide seems to oppose beta-adrenoceptor potentiation of diaphragm contractility, and such an interaction depends on previous adrenoceptor stimulation. Nitric oxide probably decreases beta-adrenoceptor response via cGMP-induced stimulation of phosphodiesterase 2. The interaction between substances which modulate NO system activity and cAMP levels in the skeletal muscle may be of a great clinical importance for the treatment of certain respiratory and neurological diseases