Lack of a role of adenosine in activation of ischemically sensitive cardiac sympathetic afferents.
Adenosine has been implicated in the pathogenesis of cardiac pain through activation of cardiac sympathetic afferents. The present study was performed to assess directly the contribution of adenosine in activating ischemically sensitive cardiac sympathetic afferents. Single-unit activity of ischemically sensitive afferents located in both ventricles was recorded from the left thoracic sympathetic chain or rami communicantes of anesthetized cats during 5 min of myocardial ischemia. Intracardiac injection (5 mg) or epicardial application (1-5 mg/ml) of adenosine onto the receptive fields failed to activate 31 ischemically sensitive A delta- and C fiber afferents, which were responsive to topical application of bradykinin (10 micrograms/ml). Intracardiac injection (5 mg) or topical application (1-5 mg/ml) of an adenosine A1 receptor agonist, N6-cyclopentyladenosine, also did not increase the discharge activity of 13 other ischemically sensitive C fiber afferents. Treatment with dipyridamole (1 mg/kg iv) to inhibit the cellular uptake of adenosine 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 significantly attenuate the response of 10 other C fiber afferents to 5 min of myocardial ischemia. The results of the present study demonstrate that 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 A1 receptors in activation of cardiac sympathetic afferents during myocardial ischemia.
Pan
H L
HL
Department of Internal Medicine, University of California, Davis 95616, USA.
Longhurst
J C
JC
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002415:Cats; D004176:Dipyridamole / Q000494:pharmacology; D004594:Electrophysiology; D006329:Heart Conduction System / Q000503:physiopathology*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009475:Neurons, Afferent / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D000628:Aminophylline; C048599:N(6)-cyclopentyladenosine; D004176:Dipyridamole; D000241:Adenosine; D001920:Bradykinin