title: Electrophysiological-anatomic correlates of ATP-triggered vagal reflex in the dog. IV. Role of LV vagal afferents.
abstract: The negative chronotropic action and the time to peak effect (t(p)) of ATP and its related analogs [2-methylthio-ATP (2-MeSATP), alpha,beta-methylene-ATP (alpha,beta-mATP), and beta,gamma-methylene-ATP (beta,gamma-mATP)] as well as ADP, AMP, and adenosine were determined in anesthetized dogs. Intra-right atrium (RA) and intra-left main coronary artery (LM) ATP markedly suppressed sinus node automaticity. ATP induced a much greater response when administered into the LM than into the RA. The t(p) of ATP administered at the former site was much shorter than that at the latter site. Intra-LM adenosine had either no effect or a relatively very small effect, and its t(p) was significantly longer than that of intra-LM ATP. Bilateral cervical vagotomy either abolished or markedly attenuated the effect of intra-RA and intra-LM ATP; under these conditions, the actions of ATP and adenosine and their t(p) values became similar. The structure-function cascade of intra-LM ATP and its analogs was alpha,beta-mATP > 2-MeSATP > ATP > or = beta,gamma-mATP > ADP >> AMP = 0. The P2X-purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid markedly attenuated the negative chronotropic action of all purine nucleotides. It was concluded that 1) ATP triggers a cardiocardiac vagal depressor reflex by stimulating vagal afferent nerve terminals in the LV myocardium and 2) this action is mediated by P2X-purinoceptors.
authors.affiliation: Likoff Cardiovascular Institute, Department of Medicine, Allegheny University of Health Sciences, Philadelphia, Pennsylvania 19102-1192, USA.
authors.forename: G
authors.initials: G
authors.lastname: Katchanov
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: A
authors.initials: A
authors.lastname: Clay
authors.forename: A
authors.initials: A
authors.lastname: Pelleg
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000294:innervation*; D004285:Dogs; D005260:Female; D006321:Heart / Q000502:physiology*; D006325:Heart Atria; D006339:Heart Rate / Q000187:drug effects*; D007269:Injections, Intra-Arterial; D008297:Male; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000502:physiology; D012018:Reflex; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
chemical_list: D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D000249:Adenosine Monophosphate; D011732:Pyridoxal Phosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000241:Adenosine