Involvement of β-adrenoceptors in the cardiovascular responses induced by selective adenosine A2A and A2B receptor agonists

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

Abstract

A2A and A2B adenosine receptors produce regionally selective regulation of vascular tone and elicit differing effects on mean arterial pressure (MAP), whilst inducing tachycardia. The tachycardia induced by the stimulation of A2A or A2B receptors has been suggested to be mediated by a reflex increase in sympathetic activity. Here, we have investigated the role of β1- and β2-adrenoceptors in mediating the different cardiovascular responses to selective A2A and A2B receptor stimulation. Hemodynamic variables were measured in conscious male Sprague-Dawley rats (350–450 g) via pulsed Doppler flowmetry. The effect of intravenous infusion (3 min per dose) of the A2A-selective agonist CGS 21680 (0.1, 0.3, 1.0 µg.kg−1.min−1) or the A2B-selective agonist BAY 60–6583 (4.0, 13.3, 40.0 µg.kg−1.min−1) in the absence or following pre-treatment with the non-selective β-antagonist propranolol (1.0 mg.kg−1), the selective β1-antagonist CGP 20712A (200 µg.kg−1), or the selective β2-antagonist ICI 118,551 (2.0 mg.kg−1) was investigated (maintenance doses also administered). CGP 20712A and propranolol significantly reduced the tachycardic response to CGS 21680, with no change in the effect on MAP. ICI 118,551 increased BAY 60–6583-mediated renal and mesenteric flows, but did not affect the heart rate response. CGP 20712A attenuated the BAY 60–6583-induced tachycardia. These data imply a direct stimulation of the sympathetic activity via cardiac β1-adrenoceptors as a mechanism for the A2A- and A2B-induced tachycardia. However, the regionally selective effects of A2B agonists on vascular conductance were independent of sympathetic activity and may be exploitable for the treatment of acute kidney injury and mesenteric ischemia.

Citation

Wragg, E. S., Pannucci, P., Hill, S. J., Woolard, J., & Cooper, S. L. (2022). Involvement of β-adrenoceptors in the cardiovascular responses induced by selective adenosine A2A and A2B receptor agonists. Pharmacology Research and Perspectives, 10(3), Article e00975. https://doi.org/10.1002/prp2.975

• Journal Article Type: Article
• Acceptance Date: May 9, 2022
• Online Publication Date: May 29, 2022
• Publication Date: May 29, 2022
• Deposit Date: Dec 17, 2022
• Publicly Available Date: Dec 20, 2022
• Journal: Pharmacology Research and Perspectives
• Print ISSN: 2052-1707
• Electronic ISSN: 2052-1707
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 10
• Issue: 3
• Article Number: e00975
• DOI: https://doi.org/10.1002/prp2.975
• Keywords: A2A receptor, A2B receptor, adenosine, hemodynamics, β- adrenoceptor
• Public URL: https://nottingham-repository.worktribe.com/output/8310052
• Publisher URL: https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/prp2.975