Inhibition by propranolol of the contractile response of the rat diaphragm to tetanic field stimulation in vitro.

Contraction of the rat isolated diaphragm in response to maximal tetanic stimulation was examined before and after isoprenaline or propranolol. Isoprenaline (10(-4)M) did not affect maximum isometric force, whereas propranolol depressed maximum force in a concentration-dependent manner (10(-6)-10(-4)M). Inhibition due to propranolol (10(-4)M) could not be overcome by increasing the intensity or duration of electrical stimulation, and was only partially reversed (mean 73% +/- 10 s.e. mean) after washing. Pretreatment with isoprenaline did not alter the response of the muscle to propranolol, nor did neuromuscular blockade with (+)-tubocurarine. The response to either stereoisomer of propranolol was similar to that obtained with the racemate. Atenolol, a beta-adrenoceptor blocking agent without membrane stabilizing activity, had minimal (less than 10%) depressant effects on diaphragmatic force development. Lignocaine (8.5 X 10(-6)-8.5 X 10(-5)M) produced a concentration-related decrease in isometric force, similar to that with propranolol. It is concluded that propranolol decreases the contractile force of the rat isolated diaphragm by a mechanism related to stabilization of excitable membranes.