Rat Heart Interstitial Adenosine

Adenosine (ADO) has an antiadrenergic action in the heart that causes an attenuation of contractile and metabolic responses elicited by fi-adrenergic stimulation. The effect of an increase in oxygen consumption elicited by either f-adrenergic stimulation or an increase in contraction frequency on interstitial fluid and coronary effluent ADO levels was investigated in isolated perfused isovolumically contracting rat hearts. ADO in left ventricular surface transudates and coronary effluents was rendered fluorescent with chloroacetaldehyde, and the formed ethenoadenosine derivative was quantitated with high-performance liquid chromatography fluorescence detection. Heart preparation integrity was verified by determining the activities of lactate dehydrogenase and ADO deaminase in the transudates. Isoproterenol (10-8 M) elicited a 45% increase in oxygen consumption and a 54% increase in developed left ventricular pressure in hearts paced at 240 beats/min. With isoproterenol the control transudate ADO concentration (304 pmol/ml) increased 493%, and the control effluent ADO concentration (48 pmol/ml) increased 259%. Increasing the contraction frequency from 180 to 300 beats/min in the presence of 10-6 M propranolol increased oxygen consumption by 45% and decreased left ventricular pressure by 291%. With the increase in contraction frequency, the transudate ADO concentration did not increase significantly. However, the ADO concentration in the effluent was an average of 269% greater in hearts contracting at the higher frequency. Increasing the contraction frequency of hearts treated with both 10-6 M propranolol and 10` M atropine also had no significant effect on the level of transudate ADO. The effluent level ofADO increased only 78%. Levels ofADO in transudates were not significantly affected by mesothelial cell metabolism. These results suggest that with /8-adrenergic stimulation the interstitial level of ADO in the heart increases to levels that are sufficient to manifest its antiadrenergic effects. Furthermore, there is not always a correlation between the levels of fluid compartments. (Circulation Research