title: Downregulation of adenosine and P2X receptor-mediated cardiovascular responses in heart failure rats.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: X H
authors.initials: XH
authors.lastname: Zhao
authors.forename: X Y
authors.initials: XY
authors.lastname: Sun
authors.forename: D
authors.initials: D
authors.lastname: Erlinge
authors.forename: L
authors.initials: L
authors.lastname: Edvinsson
authors.forename: T
authors.initials: T
authors.lastname: Hedner
mesh_terms: 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*
chemical_list: D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D000241:Adenosine