Reflex sympathoexcitation by cardiac sympathetic afferents during myocardial ischemia. Role of adenosine.
BACKGROUND
Stimulation of cardiac sympathetic afferents during myocardial ischemia has been attributed to bradykinin released from the ischemic myocardium. Recent data from human studies suggest that adenosine may serve as this mediator. Our experiments were done to determine whether reflex sympathoexcitatory responses to activation of cardiac sympathetic afferents during myocardial ischemia could be inhibited by blockade of adenosine receptors and augmented by increasing the local concentrations of adenosine in the ischemic myocardium.


RESULTS
Experiments were done in 29 anesthetized dogs with bilateral vagotomy and carotid sinus denervation. Activation of cardiac sympathetic afferent fibers was induced by occlusion of the left anterior descending coronary artery (LAD) combined with rapid atrial pacing (pacing rate, 200 beats per minute). LAD occlusion plus rapid atrial pacing increased renal sympathetic nerve activity by 20 +/- 4% before but by only 7 +/- 1% after administration of aminophylline (100 mg i.v.), an adenosine receptor antagonist. In contrast, LAD occlusion during rapid atrial pacing increased renal sympathetic nerve activity by 18 +/- 8% before and 61 +/- 15% after treatment with dipyridamole (0.57 mg/kg i.v.), an inhibitor of adenosine reuptake. In a separate group of dogs, LAD occlusion during rapid atrial pacing increased renal sympathetic nerve activity similarly before and after sham treatment.


CONCLUSIONS
These data suggest that adenosine released during myocardial ischemia activates cardiac sympathetic afferents to cause reflex sympathoexcitation. These findings are consistent with observations made in humans that suggest that adenosine is the mediator of the sensation of angina pectoris, which also results from stimulation of cardiac sympathetic afferents.
Department of Medicine, University Hospitals of Cleveland, OH 44106.
M D
MD
Thames
T
T
Kinugawa
M E
ME
Dibner-Dunlap
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000502:physiology*; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D002304:Cardiac Pacing, Artificial; D004176:Dipyridamole / Q000494:pharmacology; D004285:Dogs; D006329:Heart Conduction System / Q000473:pathology / Q000503:physiopathology*; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology*; D009475:Neurons, Afferent / Q000502:physiology*; D058914:Purinergic Antagonists; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000473:pathology / Q000503:physiopathology*
D058914:Purinergic Antagonists; D000628:Aminophylline; D004176:Dipyridamole; D000241:Adenosine