AJP - Heart and Circulatory Physiology, Vol 272, Issue 4 1898-H1903, Copyright © 1997 by American Physiological Society
Electrophysiological-anatomic correlates of ATP-triggered vagal reflex in the dog. IV. Role of LV vagal afferents
G. Katchanov, J. Xu, A. Clay and A. Pelleg
Likoff Cardiovascular Institute, Department of Medicine, Allegheny University of Health Sciences, Philadelphia, Pennsylvania 19102-1192, USA.
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.
