Adenosine inhibition of beta-adrenergic induced responses in aged hearts
Department of Physiology
5'-Nucleotidase; Adenosine; Adenosine Deaminase; Adrenergic beta-Antagonists; Aging; Animals; Coronary Vessels; Cyclic AMP; Extracellular Space; Heart; Inosine; Male; Myocardial Contraction; Myocardium; Oxygen Consumption; Phosphorylases; Rats; Rats, Inbred F344; Rats, Sprague-Dawley
Cardiovascular Diseases | Physiology
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.
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Citation: Am J Physiol. 1993 Aug;265(2 Pt 2):H494-503.