Murphy, René J. L., Phillip F. Gardiner, Guy Rousseau, Michel Bouvier, and Louise Béliveau. Chronic -blockade increases skeletal muscle -adrenergic-receptor density and enhances contractile force. J. Appl. Physiol. 83(2): 459-465, 1997.The effects of a chronic 14-day administration of a selective ₂-adrenergic-receptor antagonist (ICI-118551) on skeletal muscle were evaluated in female Sprague-Dawley rats. Chronic ICI-118551 treatment did not modify muscle mass, oxidative potential, or protein concentration of the medial gastrocnemius muscle, suggesting that maintenance of these skeletal muscle characteristics is not dependent on ₂-adrenergic-receptor stimulation. However, the drug treatment increased -adrenergic-receptor density of the lateral gastrocnemius (42%) and caused an increase in specific (g/g) isometric in situ contractile forces of the medial gastrocnemius [twitch, 56%; tetanic (200 Hz), 28%]. The elevated contractile forces observed after a chronic treatment with ICI-118551 were completely abolished when the ₂-adrenergic antagonist was also administered acutely before measurement of contractile forces, suggesting that this response is ₂-adrenergic-receptor dependent. Possible mechanisms for the increased forces were studied. Caffeine administration potentiated twitch forces but had little effect on tetanic force in control animals. Administration of dibutyryl adenosine 3,5-cyclic monophosphate in control animals also resulted in small increases of twitch force but did not modify tetanic forces. We conclude that increases in -adrenergic-receptor density and the stimulation of the receptors by endogenous catecholamines appear to be responsible for increased contractile forces but that the mechanism remains to be demonstrated.