Effect of Aging on the Negative Chronotropic and Anti-β-Adrenergic Actions of Adenosine in the Rat Heart

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Abstract
The effect of aging on the antiadrenergic actions of adenosine was studied in vitro and in vivo by using adult (6-month-old) and old (24-month-old) male Fischer 344 rats. In anesthetized animals, adenosine (0.01-0.1 μmol/kg), given as a rapid bolus into the right atrium, exerted a negative chronotropic effect manifested by a dose-dependent transient prolongation of sinus cycle length (SCL). This effect was similar in both age groups (n = 6, each; i.e., the percentage maximal prolongation of SCL (%ΔSCL) ranged from 12 ± 2% to 63 ± 14% in the adult and from 20 ± 7% to 57 ± 15% in the old rats. In the presence of isoproterenol (0.2 μg/kg/min), the negative chronotropic action of adenosine was potentiated in the adult rats much more than in the old rats [i.e., %ΔSCL ranged from 60 ± 28% to 183 ± 48% vs. 40 ± 12% to 70 ± 13%, respectively (p < 0.05, adult vs. old)]. In the isolated perfused hearts, isoproterenol (1 μM for 1 min) exerted similar chronotropic and inotropic effects in adult (n = 9) and old hearts [n = 6; i.e., heart rate, left ventricular pressure (LVP), and LVdp/dt increased by 56 ± 3%, 17 ± 1%, and 37 ± 2%, and 57 ± 2%, 17 ± 1%, and 35 ± 3%, respectively, in the absence of, and by 27 ± 2%, 7 ± 1%, and 19 ± 2% and 41 ± 3%, 12 ± 1%, and 25 ± 2% in the presence of adenosine (5 μM for 1 min)]. Adenosine administration after isoproterenol caused only an insignificant increase in coronary blood flow. Finally, the adenosine attenuation of either isoproterenol- or forskolin-induced production of 3′,5′-cyclic adenosine monophosphate (cAMP) was significantly less in atrial membranes isolated from old versus adult rats (n = 6, each). It was concluded that in the old Fischer 344 rat hearts, the antiadrenergic action of adenosine is attenuated as compared with its action in adult rat hearts.