Skip to main content

Research Repository

Advanced Search

Regionally selective cardiovascular responses to adenosine A2A and A2B receptor activation

Cooper, Samantha L.; Wragg, Edward S.; Pannucci, Patrizia; Soave, Mark; Hill, Stephen J.; Woolard, Jeanette

Regionally selective cardiovascular responses to adenosine A2A and A2B receptor activation Thumbnail


Authors

Edward S. Wragg

Patrizia Pannucci

Mark Soave

STEPHEN HILL STEVE.HILL@NOTTINGHAM.AC.UK
Professor of Molecular Pharmacology

JEANETTE WOOLARD Jeanette.Woolard@nottingham.ac.uk
Professor of Cardiovascular Physiology and Pharmacology



Abstract

Adenosine is a local mediator that regulates changes in the cardiovascular system via activation of four G protein-coupled receptors (A1, A2A, A2B, A3). Here, we have investigated the effect of A2A and A2B-selective agonists on vasodilatation in three distinct vascular beds of the rat cardiovascular system. NanoBRET ligand binding studies were used to confirm receptor selectivity. The regional hemodynamic effects of adenosine A2A and A2B selective agonists were investigated in conscious rats. Male Sprague-Dawley rats (350–450 g) were chronically implanted with pulsed Doppler flow probes on the renal artery, mesenteric artery, and the descending abdominal aorta. Cardiovascular responses were measured following intravenous infusion (3 min for each dose) of the A2A-selective agonist CGS 21680 (0.1, 0.3, 1 µg kg−1 min−1) or the A2B-selective agonist BAY 60-6583 (4,13.3, 40 µg kg−1 min−1) following predosing with the A2A-selective antagonist SCH 58261 (0.1 or 1 mg kg−1 min−1), the A2B/A2A antagonist PSB 1115 (10 mg kg−1 min−1) or vehicle. The A2A-selective agonist CGS 21680 produced a striking increase in heart rate (HR) and hindquarters vascular conductance (VC) that was accompanied by a significant decrease in mean arterial pressure (MAP) in conscious rats. In marked contrast, the A2B-selective agonist BAY 60-6583 significantly increased HR and VC in the renal and mesenteric vascular beds, but not in the hindquarters. Taken together, these data indicate that A2A and A2B receptors are regionally selective in their regulation of vascular tone. These results suggest that the development of A2B receptor agonists to induce vasodilatation in the kidney may provide a good therapeutic approach for the treatment of acute kidney injury.

Citation

Cooper, S. L., Wragg, E. S., Pannucci, P., Soave, M., Hill, S. J., & Woolard, J. (2022). Regionally selective cardiovascular responses to adenosine A2A and A2B receptor activation. FASEB Journal, 36(4), Article e22214. https://doi.org/10.1096/fj.202101945R

Journal Article Type Article
Acceptance Date Feb 7, 2022
Online Publication Date Mar 1, 2022
Publication Date Mar 1, 2022
Deposit Date Dec 17, 2022
Publicly Available Date Mar 28, 2024
Journal FASEB Journal
Print ISSN 0892-6638
Electronic ISSN 1530-6860
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 36
Issue 4
Article Number e22214
DOI https://doi.org/10.1096/fj.202101945R
Keywords A2 receptor activation, adenosine, Doppler flow, hemodynamics
Public URL https://nottingham-repository.worktribe.com/output/7537865
Publisher URL https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202101945R

Files




You might also like



Downloadable Citations