ADENOSINE ACTIVATES CARDIAC SYMPATHETIC AFFERENT-FIBERS AND POTENTIATES THE EXCITATION INDUCED BY CORONARY-OCCLUSION

Adenosine is a possible mediator of cardiac pain during myocardial isc hemia; however, little is known about the influence of adenosine on ca rdiac sympathetic afferent activity and thereby on its algogenic mecha nism. In 20 anaesthetized, decerebrated, curarized and artificially ve ntilated cats, we studied the impulse activity of 20 single afferent s ympathetic fibers with a left ventricular receptive field in relation to epicardial applications of adenosine, coronary artery occlusions an d arterial pressure rises. All fibers increased. their impulse activit y (from 1.2 +/- 0.2 to 2.6 +/- 0.5 imp/s; P < 0.001) during slight (20 +/- 8%) rises in aortic pressure, thus exhibiting low-threshold recep tor characteristics. In 10 cats, epicardial applications of three diff erent doses of adenosine (0.1, 1 and 10 mg/ml) caused a brief increase in neural activity with dose-related responses. This response was abo lished by aminophylline, a P-1 purinergic inhibitor. In the other grou p of 10 cats, four subsequent 30-s occlusions of the coronary arterial vessel supplying the receptive fields of the fibers were performed, i n control conditions and 30 s, 3 and 7 min, respectively, after the en d of excitation induced by adenosine (1 mg/ml) application. During the control coronary occlusion the impulse activity increased from 1.1 +/ - 0.1 to 5.5 +/- 0.7 imp/s (P < 0.0001). A similar activation was pres ent during the second occlusion initiated 30 s after the end of adenos ine-induced activation. In contrast, a significant potentiation of the response was observed (8.8 +/- 1.2 vs. 5.3 +/- 0.9 imp/s; P < 0.001) during the occlusion initiated 3 min after the end of excitation by ad enosine. This effect was no longer present during the last occlusion p erformed after 7 min. When the protocol was repeated substituting aden osine with saline (n = 5) or after i.v. administration of aminophyllin e (n = 5), no potentiation was observed, even though the excitatory re sponse to coronary occlusion was preserved. These data show that adeno sine can activate cardiac sympathetic afferent fibers in a dose-relate d manner, and potentiate their responses to coronary occlusion, while leaving unaffected the responsiveness to a hemodynamic stimulus. The e xcitatory effects are likely to involve the P-1 purinergic receptors. The potentiation phenomenon might play a role in the genesis of an alg ogenic code.