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

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Abstract
1 Contraction of the rat isolated diaphragm in response to maximal tetanic stimulation was examined before and after isoprenaline or propranolol. 2 Isoprenaline (10−4m) did not affect maximum isometric force, whereas propranolol depressed maximum force in a concentration-dependent manner (10−6-10−4m). 3 Inhibition due to propranolol (10−4m) 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. 4 Pretreatment with isoprenaline did not alter the response of the muscle to propranolol, nor did neuromuscular blockade with (+)-tubocurarine. 5 The response to either stereoisomer of propranolol was similar to that obtained with the racemate. 6 Atenolol, a β-adrenoceptor blocking agent without membrane stabilizing activity, had minimal (< 10%) depressant effects on diaphragmatic force development. 7 Lignocaine (8.5 × 10−6-8.5 × 10−5m) produced a concentration-related decrease in isometric force, similar to that with propranolol. 8 It is concluded that propranolol decreases the contractile force of the rat isolated diaphragm by a mechanism related to stabilization of excitable membranes.