Chronic beta -blockade increases skeletal muscle beta -adrenergicreceptor density and enhances contractile force

Murphy, René J. L., Phillip F. Gardiner, Guy Rousseau,Michel Bouvier, and Louise Béliveau. Chronic -blockadeincreases skeletal muscle -adrenergic-receptor density and enhancescontractile force. J. Appl. Physiol.83(2): 459-465, 1997.The effects of a chronic 14-dayadministration of a selective₂-adrenergic-receptor antagonist (ICI-118551) on skeletal muscle were evaluated in female Sprague-Dawley rats. Chronic ICI-118551 treatment did not modify musclemass, oxidative potential, or protein concentration of the medialgastrocnemius muscle, suggesting that maintenance of these skeletalmuscle characteristics is not dependent on₂-adrenergic-receptor stimulation. However, the drug treatment increased-adrenergic-receptor density of the lateral gastrocnemius (42%) andcaused an increase in specific (g/g) isometric in situ contractileforces of the medial gastrocnemius [twitch, 56%; tetanic (200 Hz), 28%]. The elevated contractile forces observed after achronic treatment with ICI-118551 were completely abolished when the₂-adrenergic antagonist wasalso administered acutely before measurement of contractile forces,suggesting that this response is₂-adrenergic-receptor dependent. Possible mechanisms for the increased forces were studied. Caffeine administration potentiated twitch forces but had little effecton tetanic force in control animals. Administration of dibutyryladenosine 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 endogenouscatecholamines appear to be responsible for increased contractileforces but that the mechanism remains to be demonstrated.