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Cardiovascular Research 2002 53(4):888-901; doi:10.1016/S0008-6363(01)00542-9
© 2002 by European Society of Cardiology
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Copyright © 2002, European Society of Cardiology

Role of P1 purinergic receptors in myocardial ischemia sensory transduction

G.W Thompsona, M Horackovaa and J.A Armoura,*

aDepartment of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada

jarmour{at}is.dal.ca

* Corresponding author. Tel.: +1-902-494-3382; fax: +1-902-494-1685

Objectives: To characterize the role that cardiac sensory P1 purinergic (adenosine A1 or A2) receptors play in transducing myocardial ischemia. Methods: Porcine nodose ganglion cardiac sensory neuron adenosine A1 or A2 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 A1 or A2 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 P1 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 A1 and/or A2 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.

KEYWORDS Adenosine; Autonomic nervous system; Ischemia; Receptors


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