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) male Fischer 344 rats. In anesthetized animals, adenosine (0.01-0.1 micromol/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 (%deltaSCL) 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 microg/kg/min), the negative chronotropic action of adenosine was potentiated in the adult rats much more than in the old rats [i.e., %deltaSCL 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 microM 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 microM 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.
Xu
J
J
Department of Medicine, Allegheny University of Health Sciences, Philadelphia, Pennsylvania, USA.
Gao
F
F
Ma
X L
XL
Gao
E
E
Friedman
E
E
Snyder
D L
DL
Horwitz
J
J
Pelleg
A
A
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D004562:Electrocardiography / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000166:cytology; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D011916:Rats, Inbred F344; D018047:Receptors, Purinergic P1 / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D002317:Cardiovascular Agents; C109113:N(6)-(4-sulfophenyl)adenosine; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D005576:Colforsin; D000241:Adenosine