Antiadrenergic Action sof Adenosine in the Heart: Possible Physiological Significance
Adenosine was recently demonstrated by us to attenuate the inotropic and glycogenolytic effects of catecholamines in the guines pig heart . In an attempt to further characterize this effect, the influence of adenosine on cardiac contractility and adenylate cyclase activity stimulated by isoproterenol (ISO), histamine (H), and dopamine (DOP) was studied. Furthermore, the possible role of endogenously formed adenosine in modulating the response of the heart to β-adrenergic stimulation was investigated.
Adenosine applied to the isolated perfused guinea pig heart produced a dose-dependent inhibition of contractile force development elicited by bolus injections of ISO, H, and DOP. The action of adenosine was rapid in onset and fully reversible. In a particulate membrane preparation of ventricular tissue the adenylate cyclase activity stimulated by ISO, H, and DOP was inhibited by adenosine and this effect could be reversed by theophilline.
Reduction of perfusion pressure from 60 to 40 and 20 cm H20 diminished the contractile responsiveness of the heart to isoproterenol. This condition was associated with a progressive increase in the concentration of adenosine in the coronary effluent perfusate. Time course of release of adenosine correlated well with the diminished inotropic response, and the concentrations of adenosine were in the catecholamine-antagonistic range. Similar results were obtained when hearts were perfused with a hypoxic medium.
Our findings suggest that adenosine formed by the heart may act as an important negative feedback-inhibitor of the actions of catecholamines, thus preventing sympathetic overstimulation of the heart.
KeywordsAdenylate Cyclase Contractile Force Adenylate Cyclase Activity Adenosine Derivative Myocardial Cell Membrane
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