EFFECT OF ADENOSINE ON HEART-RATE IN ISOLATED MUSKRAT AND GUINEA-PIG HEARTS

The purpose of this study was to co pare the responses of isolated hea rts of the diving muskrat wit the nondiving guinea pig (GP) to determi ne the contribution adenosine (ADO) to the profound bradycardia that w as seen in isolated muskrat hearts during exposure to hypoxia. Muskrat hearts were more sensitive than GP hearts to the heart rate-lowering effects of exogenously applied ADO or a stable AD analogue, (R)-N6-(ph enylisopropyl)adenosine. The hearts both species were unpaced, and the bradycardia appeared to b due to high degree of atrioventricular bloc k. Radioligand binding with 8-cyclopentyl-1,3-[H-3]dipropylxanthine to A1-ADO receptors was greater in cardiac membranes prepared from G hea rts than from muskrat hearts. Nucleoside transporter antagonist bindin g was also greater in GP hearts compared with muskrats. This was deter mined by membrane binding of [H-3]-nitrobenzylthioinosine, an antagoni st of nucleoside transport. Both muskrat and GP hearts responded to 30 min of hypoxic perfusion by releasing ADO into the coronary effluent; however the muskrat hearts released approximately five times more tha n the GP hearts. When hearts were subjected to hypoxia in the presence of ADO deaminase, theophylline, or 8-(p-sulfophenyl)theophylline, the hypoxia-induced bradycardia was blocked in the GP hearts and either s lightly reduced or no affected in muskrat hearts. In contrast to GP he arts, muskrat hearts release larger amounts of ADO during hypoxia and are more sensitive to the negative chronotropic effects of exogenously administered ADO; yet the hypoxia-induced bradycardia does not appear to be exclusively mediated by ADO in the muskrat as it is in the isol ated GP heart.