Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA015

Poster Communications

Loss of cross-talk between atrial A1 and A2A Adenosine receptors upon continuous atrial pacing and autonomic stimulation

M. Carvalho1, S. Laranjo1,2, M. M. Oliveria2, I. Rocha1,2

1. Cardiovascular Center of University of Lisbon, Lisboa, Portugal. 2. Physiology Institute, Faculty of Medicine of University of Lisbon, Lisbon, Portugal.

Adenosine is a natural occurring nucleoside throughout most of the body systems, resulting from the biological process of consuming ATP (energy). In the cardiovascular system, more specifically in the myocardium, adenosine exerts a well established protective action during myocardial ischemia and reperfusion injury, as well as, in several other conditions of stress, such as the ageing process and infection. These protective actions are mediated via activation of specific receptor subtypes (adenosine receptors A1, A2A, A2B and A3). In addition, there is also increasing evidence that optimal adenosine cardioprotection requires the activation of more than one receptor subtype. Hence, the purpose of the current study was to determine whether the cross-talk between adenosine A2A and A1 receptors modulate receptor-mediated protection in conditions of cardiac rhythm changes, induced by strong autonomic activation. We have employed real-time PCR to rapidly and sensitively determine specific adenosine receptor transcript levels, resulting from continuous atrial high frequency pacing and autonomic activation (Sympathetic and Vagal stimulation isolated or combined), in both atria and ventricles from a total of 20 Wistar rats (11 to 14 wks). Briefly, the animals were anaesthetized with sodium pentobarbitone (60 mg/Kg; ip), and supplemented with 20% solution (iv), followed by neuromuscular blockade (Norcuron, 0.05 mg/kg/h, iv). Blood pressure, ECG, and body temperature were continuously monitored. Animals were randomized in five experimental groups. Control: no stimulation; Group 2: 2h high frequency atrial pacing at the right side, with a concentric bipolar microelectrode; Group 3: 2h continuous right cervical vagus nerve stimulation; Group 4: 2h continuous thoracic sympathetic trunk stimulation; Group 5: 2h Vagal and sympathetic stimulation. Relative quantification using the housekeeping gene 18S rRNA as internal control, revealed no significant changes in the levels of A1 mRNA and a very significant increase of A2A expression levels for all types of stimulation, in both atria and ventricles (p≤0.0065 vagal and sympathetic stimulation; p<0.0001 for dual stimulation and atrial pacing). As expected, the present findings emphasize the already important adenosinergic cardioprotective action of the adenosine receptors studied herein, suggesting a marked activation of the adenosine receptor A2A as a primary response against both physical and physiological strain and sinus rhythm modulations due to ANS stimulation, which may contribute to the recovery of the myocardium cells, preventing further inflammation downstream the remodeling mechanisms.

Where applicable, experiments conform with Society ethical requirements