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Differential Modulation by Adenosine A 1 and A 3 Receptors of Acute Endotoxemia‐Induced Hemodynamics, Cardiac Autonomic Impairment, and Oxidative Damage

Title: Differential Modulation by Adenosine A 1 and A 3 Receptors of Acute Endotoxemia‐Induced Hemodynamics, Cardiac Autonomic Impairment, and Oxidative Damage
Authors: El‐Yazbi, Ahmed F.; Fouda, Mohammed; Mroueh, Ali; El‐Mas, Mahmoud M
Source: The FASEB Journal ; volume 33, issue S1 ; ISSN 0892-6638 1530-6860
Publisher Information: Wiley
Publication Year: 2019
Collection: Wiley Online Library (Open Access Articles via Crossref)
Description: We and others have previously reported that endotoxemia elicits detrimental cardiac autonomic and hemodynamic consequences. Despite the recognized roles of adenosine and its receptors in central and peripheral cardiovascular control, the contribution of adenosine receptors in the hemodynamic and autonomic sequalae of endotoxemia remains largely unknown. In this study, we examined whether selective A 1 or A 3 receptor stimulation would modify the hemodynamic and autonomic responses to acute exposure to lipopolysaccharide (LPS). Rats were instrumented for conscious invasive hemodynamic recording through femoral indwelling catheters. Rats were injected with LPS (5 mg/kg i.v.) and variation in blood pressure (BP), heart rate (HR), left ventricular systolic and diastolic functions (dP/dt max and tau, respectively), and frequency domain parameters (HF & LF power and LF/HF) of heart rate variability (HRV) were recorded over two hours. The modifying effect of two doses of A 1 ‐ (CPA, 75 and 300 μg/Kg) or A 3 ‐agonists (IB‐MECA 25 and 50 μg/Kg) were studied. As expected, LPS injection was associated with falls in BP, reflex tachycardia, and increased systolic contractility; however cardiac sympathetic impairment was evident as reduced LF power and sympathovagal balance. A 3 receptor stimulation by IB‐MECA caused dose‐dependent counteraction of the hypotensive effect of LPS as well as the associated positive chronotropism and increased systolic contractility. The LPS‐evoked decreases in LF power of HRV and shift in sympathovagal balance towards parasympathetic dominance were also reversed by IB‐MECA. Alternatively, all the LPS actions, but the hypotension, disappeared upon concurrent stimulation of A 1 receptor (CPA). We also show that except the improved sympathovagal balance, the favorable effects of CPA or IB‐MECA on LPS responses were eliminated after selective antagonism of their respective receptors. Significantly, signs of left ventricular focal ischemia and elevated myocardial oxidative stress triggered by LPS ...
Document Type: article in journal/newspaper
Language: English
DOI: 10.1096/fasebj.2019.33.1_supplement.513.2
Availability: http://dx.doi.org/10.1096/fasebj.2019.33.1_supplement.513.2
Rights: http://onlinelibrary.wiley.com/termsAndConditions#vor
Accession Number: edsbas.15F89082
Database: BASE