Effect of aging on rat skeletal muscle beta-AR function in male Fischer 344 x brown Norway rats.
In this study, we tested the hypothesis that, in the male Fischer 344 x Brown Norway (F344xBN) rat, aging would be associated with an increase in sympathetic nervous system activity and a decrease in skeletal muscle beta-adrenergic-receptor (beta-AR) density and function. Radioligand-binding studies using [125I] iodocyanopindolol were done to evaluate beta-AR density (Bmax) and antagonist-binding affinity in gastrocnemius and cardiac muscle from 6-, 18-, and 28-mo-old male F344xBN rats. beta-AR function was measured as adenylyl cyclase (AC) activity stimulated by the beta-AR agonist isoproterenol (Iso, 10(-4) M). Basal arterial plasma norepinephrine (pNE) concentrations were higher in the 28-than in the 6- and 18-mo-old rats. Bmax was greatest and Iso-stimulated AC activity was unchanged in gastrocnemius muscle of the 28-mo-old age group. In contrast, there was an age-associated decrease in Bmax and Iso-stimulated AC activity in cardiac muscle. In conclusion, there was an age-associated increase in pNE concentrations in male F344xBN rats, suggesting an increase in sympathetic nervous system activity. In addition, there was an age-associated increase in skeletal muscle beta-AR density, whereas in skeletal muscle beta-AR-stimulated AC activity remained unchanged with age.
Larkin
L M
LM
Department of Internal Medicine, and Institute of Gerontology, University of Michigan, Ann Arbor, USA.
Halter
J B
JB
Supiano
M A
MA
D000262:Adenylyl Cyclases / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D004837:Epinephrine / Q000097:blood; D006824:Hybridization, Genetic; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases; D009638:Norepinephrine; D004837:Epinephrine