LACK OF A ROLE OF ADENOSINE IN ACTIVATION OF ISCHEMICALLY SENSITIVE CARDIAC SYMPATHETIC AFFERENTS

Adenosine has been implicated in the pathogenesis of cardiac pain thro ugh activation of cardiac sympathetic afferents. The present study was performed to assess directly the contribution of adenosine in activat ing ischemically sensitive cardiac sympathetic afferents. Single-unit activity of ischemically sensitive afferents located in both ventricle s was recorded from the left thoracic sympathetic chain or rami commun icantes of anesthetized cats during 5 min of myocardial ischemia. Intr acardiac injection (5 mg) or epicardial application (1-5 mg/ml) of ade nosine onto the receptive fields failed to activate 31 ischemically se nsitive A delta- and C fiber afferents, which were responsive to topic al application of bradykinin (10 mu g/ml). Intracardiac injection (5 m g) or topical application (1-5 mg/ml) of an adenosine A(1) receptor ag onist, N-6-cyclopentyladenosine, also did not increase the discharge a ctivity of 13 other ischemically sensitive C fiber afferents. Treatmen t with dipyridamole (1 mg/kg iv) to inhibit the cellular uptake of ade nosine did not significantly potentiate the response of 10 separate C fiber afferents to 5 min of myocardial ischemia. Furthermore, blockade of adenosine receptors with aminophylline (5 mg/kg iv) did not signif icantly attenuate the response of 10 other C fiber afferents to 5 min of myocardial ischemia. The results of the present study demonstrate t hat exogenous and endogenous adenosine do not contribute to activation of ischemically sensitive cardiac sympathetic afferents. The findings of the present study fail to support a substantial role for adenosine and its A(1) receptors in activation of cardiac sympathetic afferents during myocardial ischemia.