CHRONIC BETA-BLOCKADE INCREASES SKELETAL-MUSCLE BETA-ADRENERGIC-RECEPTOR DENSITY AND ENHANCES CONTRACTILE-FORCE

The effects of a chronic 14-day administration of a selective beta(2)- adrenergic-receptor antagonist (ICI-118551) on skeletal muscle were ev aluated in female Sprague-Dawley rats. Chronic ICI-118551 treatment di d not modify muscle mass, oxidative potential, or protein concentratio n of the medial gastrocnemius muscle, suggesting that maintenance of t hese skeletal muscle characteristics is not dependent on beta(2)-adren ergic-receptor stimulation. However, the drug treatment increased beta -adrenergic-receptor density of the lateral gastrocnemius (42%) and ca used an increase in specific (g/g) isometric in situ contractile force s of the medial gastrocnemius [twitch, 56%; tetanic (200 Hz), 28%]. Th e elevated contractile forces observed after a chronic treatment with ICI-118551 were completely abolished when the beta(2)-adrenergic antag onist was also administered acutely before measurement of contractile forces, suggesting that this response is beta(2)-adrenergic-receptor d ependent. Possible mechanisms for the increased forces were studied. C affeine administration potentiated twitch forces but had little effect on tetanic force in control animals. Administration of dibutyryl aden osine 3',5'-cyclic monophosphate in control animals also resulted in s mall increases of twitch force but did not modify tetanic forces. We c onclude that increases in beta-adrenergic-receptor density and the sti mulation of the receptors by endogenous catecholamines appear to be re sponsible for increased contractile forces but that the mechanism rema ins to be demonstrated.