Adenosine reduces catecholamine contractile responses in oxygenated and hypoxic atria

Abstract

The properties of adenosine attenuation of catecholamine-elicited increases in peak contractile force, rate of force development, and rate of relaxation were studied in isolated rat atria. Adenosine, at a concentration that did not cause a direct depressant effect by itself, was capable of reducing by approximately 15% the increase in the contractile parameters elicited by isoproterenol. This reduction was not overcome by elevating the catecholamine concentration. The adenosine reduction was prevented by theophylline or the presence of adenosine deaminase. The reduction appears to be independent of the acetylcholine-mediated reduction of catecholamine responses. Adenosine reduced the positive inotropic responses elicited by norepinephrine and epinephrine but not phenylephrine. Adenosine deaminase in oxygenated atria potentiated the catecholamine-elicited contractile responses and reduced the progressive fall of the elevated contractile responses observed with continual catecholamine stimulation. In hypoxic atria adenosine deaminase potentiated the positive inotropic responses observed with catecholamine stimulation. The results suggest that an adenosine-specific mechanism is capable of attenuating the elevation in contractility elicited by beta-adrenergic stimulation. In addition, endogenous adenosine may be responsible, in part, for the reduction of catecholamine-mediated contractile responses in oxygenated and hypoxic myocardial tissue.