Role of P(1) purinergic receptors in myocardial ischemia sensory transduction.
OBJECTIVE
To characterize the role that cardiac sensory P(1) purinergic (adenosine A(1) or A(2)) receptors play in transducing myocardial ischemia.


METHODS
Porcine nodose ganglion cardiac sensory neuron adenosine A(1) or A(2) receptor function was studied in situ during control states as well as in the presence of the peptides bradykinin and substance P or focal ventricular ischemia. The responses of porcine nodose ganglion cardiac and non-cardiac afferent neuronal somata to adenosine were also studied in vitro.


RESULTS
Local application of A(1) or A(2) adenosine receptor agonists modified the activity generated by ventricular sensory neurites associated with 70 and 74% of identified nodose ganglion cardiac afferent somata in situ, respectively, exciting most neurons. In contrast, adenosine reduced the excitability of nodose ganglion cardiac afferent neuronal somata in vitro. Bradykinin and substance P affected 56 and 63%, respectively, of tested afferent neurons. The capacity of ventricular sensory neurites to transduce signals relating to these peptides was virtually eliminated by the presence of P(1) purinergic receptor antagonists. So was their capacity to transduce focal ventricular ischemia. Since most cardiac sensory neurites responded differently to adenosine in vivo than did cardiac afferent neuronal somata in vitro, it appears that the transduction properties of cardiac afferent neurons need to be characterized in situ.


CONCLUSIONS
Most ventricular sensory neurites associated with nodose ganglion afferent neurons possess adenosine A(1) and/or A(2) receptors that play a primary role in transducing myocardial ischemic events to central neurons. These data support clinical observations implicating cardiac sensory purinoceptors in transducing myocardial ischemic events.
Thompson
G W
GW
Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada.
Horackova
M
M
Armour
J A
JA
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002478:Cells, Cultured; D004594:Electrophysiology; D005260:Female; D006321:Heart / Q000294:innervation*; D006352:Heart Ventricles / Q000294:innervation; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D015398:Signal Transduction; D013373:Substance P / Q000494:pharmacology; D013552:Swine
D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D013373:Substance P; C048599:N(6)-cyclopentyladenosine; D000241:Adenosine; D001920:Bradykinin