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 beta2-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 beta2-adrenergic-receptor stimulation. However, the drug treatment increased beta-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 beta2-adrenergic antagonist was also administered acutely before measurement of contractile forces, suggesting that this response is beta2-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 beta-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.
Murphy
R J
RJ
Département d'Education Physique, Université de Montréal, Montreal, Quebec, Canada H3C 3J7.
Gardiner
P F
PF
Rousseau
G
G
Bouvier
M
M
Béliveau
L
L
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D005260:Female; D007537:Isometric Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551