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 increa se in sympathetic nervous system activity and a decrease in skeletal m uscle beta-adrenergic-receptor (beta-AR) density and function. Radioli gand-binding studies using [I-125]iodocyanopindolol were done to evalu ate beta-AR density (B-max) and antagonist-binding affinity in gastroc nemius and cardiac muscle from 6-, 18-, and 28-mo-old male F344xBN rat s. beta-AR function was measured as adenylyl cyclase (AC) activity sti mulated by the P-AR agonist isoproterenol (Iso, 10(-4) M). Basal arter ial plasma norepinephrine (pNE) concentrations were higher in the 28- than in the 6- and 18-mo-old rats. B-max was greatest and Iso-stimulat ed AC activity was unchanged in gastrocnemius muscle of the 28-mo-old age group. In contrast, there was an age-associated decrease in B-max 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. I n addition, there was an age-associated increase in skeletal muscle be ta-AR density, whereas in skeletal muscle beta-AR-stimulated AC activi ty remained unchanged with age.