Dl. Snyder et al., EFFECT OF AGING ON A(1)-ADENOSINE RECEPTOR-MEDIATED INHIBITION OF NOREPINEPHRINE RELEASE IN THE RAT-HEART, Journal of cardiovascular pharmacology, 31(3), 1998, pp. 352-358
Adenosine inhibits norepinephrine (NE) release from cardiac adrenergic
nerves and reduces the postsynaptic beta-adrenergic mediated actions
of NE, leading to decreased myocardial force of contraction. The actio
ns of adenosine are mediated by pre- and postsynaptic adenosine A(1) r
eceptors (A(1)-AdoR). We reported that adenosine inhibition of postsyn
aptic beta-adrenergic receptor-mediated cyclic adenosine monophosphate
(cAMP) production declines with age in male F344 rat hearts. In this
study, cardiac synaptosomes, isolated intact adrenergic nerve terminal
s, were used to examine the effect of age on adenosine inhibition of N
E release. Cardiac synaptosomes were prepared from the hearts of 6- an
d 24-month-old male F344 rats, loaded with [H-3]NE, and placed in a su
perfusion system. [H-3]NE release was induced by high [K+] exposure in
the presence of varying concentrations of adenosine or the specific A
(1)-AdoR agonist, N-6-p-sulfophenyladenosine (SPA). [H-3]NE release wa
s significantly reduced in old rats compared with young rats. Inhibiti
on of [H-3]NE release by adenosine and SPA was significantly greater i
n young rats compared with old rats. The A(1)-AdoR antagonist, 8-(p-su
lfophenyl)-theophylline, blocked the actions of adenosine on [H-3]NE r
elease, and the specific adenosine A(2)-receptor agonist, cyclopropylc
arboxamidoadenosine, had no effect on [H-3]NE release. Our data sugges
t that presynaptic A(1)-AdoR-mediated inhibition of NE release in the
rat heart declines with age.