Effect of aging on the negative chronotropic and anti-beta-adrenergic actions of adenosine in the rat heart

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) ma le Fischer 344 rats. In anesthetized animals, adenosine(0.01-0.1 mu mol/kg) , given as a rapid bolus into the right atrium, exerted a negative chronotr opic 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 (%Delta SCL) ranged from 12 +/- 2% to 63 +/- 14% in the adult and from 20 +/- 7% to 57 +/- 15% in t he old rats. In the presence of isoproterenol (0.2 mu g/kg/min), the negati ve chronotropic action of adenosine was potentiated in the adult rats much more than in the old rats [i.e., %Delta SCL 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 mu M for 1 min) exerte d similar chronotropic and inotropic effects in adult (n = 9) and old heart s [n = 6; i.e., heart rate, left ventricular pressure (LVP), and LVdp/dt in creased by 56 +/- 3%, 17 +/- 1%, and 37 +/- 2%, and 57 +/- 2%, 17 +/- 1%, a nd 35 +/- 3%, respectively, in the absence of, and by 27 +/- 2%, 7 +/- 1% a nd 19 +/- 2% and 41 +/- 3%, 12 +/- 1%, and 25 +/- 2% in the presence of ade nosine (5 mu M for I min)]. Adenosine administration after isoproterenol ca used only an insignificant increase in coronary blood flow. Finally, the ad enosine attenuation of either isoproterenol- or forskolin-induced productio n 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 .