Downregulation of adenosine and P2X receptor-mediated cardiovascular responses in heart failure rats.
Neurohormonal changes in congestive heart failure (CHF) include an enhanced peripheral sympathetic nerve activity which results in increased release of noradrenaline, neuropeptide Y and ATP. To examine if such changes in CHF would modulate peripheral pre- and postsynaptic receptors of ATP and its degradation product adenosine, experiments were performed in a rat model of ischaemic CHF. In this model, ischaemia was induced in rats by ligation of the left coronary artery. Our results demonstrate that there is a selective downregulation of P2X receptor-mediated pressor effects, while the hypotensive effects mediated by the endothelial P2Y receptors are unaffected in CHF. Moreover, the adenosine-mediated inhibitory effects on heart rate and blood pressure were also attenuated in the CHF rats. The most important changes in adenosine and P2-receptor function induced by ischaemic CHF were the reduced pressor effect mediated by the P2X receptor and the increased heart rate due to an attenuated inhibitory effect of adenosine.
Zhao
X H
XH
Department of Clinical Pharmacology, Sahlgrenska University Hospital, Göteborg, Sweden.
Sun
X Y
XY
Erlinge
D
D
Edvinsson
L
L
Hedner
T
T
D000241:Adenosine / Q000494:pharmacology / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000503:physiopathology*; D003655:Decerebrate State / Q000503:physiopathology; D015536:Down-Regulation; D004558:Electric Stimulation; D005724:Ganglia / Q000503:physiopathology; D006333:Heart Failure / Q000150:complications / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000502:physiology*
D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D000241:Adenosine