Adenosine inhibition of beta-adrenergic induced responses in aged hearts.
Because adenosine has an antiadrenergic action in the heart, young (3-4 mo) and aged (18-20 mo) adult Sprague-Dawley and Fischer 344 rat hearts were perfused to determine whether interstitial adenosine plays a role in the reduced metabolic and mechanical responsiveness of the aged heart to beta-adrenergic stimulation. Interstitial adenosine was approximately twofold greater in aged hearts compared with young adult hearts, and 10(-8) M isoproterenol (ISO) further increased these levels. ISO increased myocardial adenosine 3',5'-cyclic monophosphate content, glycogen phosphorylase activity, and cardiac contractility by 83, 150, and 130%, respectively, in young hearts but only increased these variables by 45, 74, and 61%, respectively, in aged hearts. Sulfophenyl-theophylline prevented the reduced ISO-induced responsiveness of the above variables in aged hearts. Exogenously administered adenosine deaminase eliminated the reduced ISO-induced contractile responsiveness in aged hearts. The apparent activities of 5'-nucleotidase and adenosine deaminase were not significantly different in ventricular samples from young and aged hearts. These results suggest that the elevated interstitial level of adenosine exerts a greater antiadrenergic effect in the aged heart, rendering it less responsive to beta-adrenergic stimulation. The increased interstitial level of adenosine in the aged heart does not appear to be due to a difference in the activities of either 5'-nucleotidase or adenosine deaminase.
Dobson
J G
JG
Department of Physiology, University of Massachusetts Medical School, Worcester 01655.
Fenton
R A
RA
D015720:5'-Nucleotidase / Q000378:metabolism; D000241:Adenosine / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D003331:Coronary Vessels; D000242:Cyclic AMP / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007288:Inosine / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley
D000319:Adrenergic beta-Antagonists; D007288:Inosine; D000242:Cyclic AMP; D006005:Phosphorylases; D015720:5'-Nucleotidase; D000243:Adenosine Deaminase; D000241:Adenosine