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\begin{document}

\title{The effect of the adenosine A2A and A2B selective agonists, CGS 21680
and BAY 60-6583, on regional cardiovascular haemodynamics in conscious
rats.}



\author[1]{Samantha Cooper}%
\author[1]{Edward Wragg}%
\author[1]{Patrizia Pannucci}%
\author[1]{Mark Soave}%
\author[1]{Stephen Hill}%
\author[1]{Jeanette Woolard}%
\affil[1]{University of Nottingham}%


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  \date{May 25, 2024}


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\begin{abstract}
Background and Purpose: 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. Experimental
Approach: The regional haemodynamic effects of adenosine A2A and A2B
selective agonists were investigated in conscious rats. Male
Sprague-Dawley rats (350-450g) 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 CGS 21680 (0.1,
0.3, 1 ?g.kg-1.min-1) or BAY 60-6583 (4,13.3, 40 ?g.kg-1.min-1)
following pre-dosing with either SCH 58261 (0.1 or 1 mg.kg-1.min-1), PSB
1115 (10 mg.kg-1.min-1) or vehicle. Key Results: 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. Conclusions and Implications: 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.%
\end{abstract}%



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