Key result
A2A and A2B receptors drive adenosine-induced coronary flow, while A1, A2A, and A3 regulate cardiac function.
Why the study?
Does bolus adenosine injection affect coronary blood flow and cardiac function differently across various adenosine receptor knockout mice?
Does bolus adenosine injection affect coronary blood flow and cardiac function differently across various adenosine receptor knockout mice?
In vivo ultrasound imaging in knockout mice confirms that A2 adenosine receptors regulate coronary blood flow, while A2B and A3 receptors may mediate decreases in cardiac output and stroke volume.
Does not support changes in adenosine use; leaves open receptor-specific mechanisms for human coronary and cardiac effects.
Bolus injections of adenosine and the A2A adenosine receptor (AR) selective agonist (regadenoson) are used clinically as a substitute for a stress test in people who cannot exercise. Using isolated tissue preparations, our lab has shown that coronary flow and cardiac effects of adenosine are mostly regulated by the AR subtypes A1, A2A, and A2B In this study, we used ultrasound imaging to measure the in vivo effects of adenosine on coronary blood flow (left coronary artery) and cardiac function in anesthetized wild-type, A1 knockout (KO), A2AKO, A2BKO, A3KO, A1, and A3 double KO (A1/3 DKO) and A2A and A2B double KO (A2A/2B DKO) mice in real time. Echocardiographic and Doppler studies were performed using a Visualsonic Vevo 2100 ultrasound system. Coronary blood flow (CBF) baseline data were obtained when animals were anesthetized with 1% isoflourane. Diameter (D) and velocity time integral (VTI) were measured on the left coronary arteries (CBF = ((π/4) × D(2) × VTI × HR)/1000). CBF changes were the highest within 2 min of injection (about 10 mg/kg). Heart rate, cardiac output, and stroke volume were measured by tracing the left ventricle long axis. Our data support a role for the A2 AR in CBF and further support our conclusions of previous studies from isolated tissues. Adenosine-mediated decreases in cardiac output and stroke volume may be A2B and/or A3 AR-mediated; however, the A1 and A2 ARs also play roles in overall cardiac function. These data further provide a powerful translational tool in studying the cardiovascular effects of adenosine in disease states.
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Teng et al. (2016) studied Cardiovascular effects of adenosine (n=55). Bolus adenosine injection vs. Baseline and wild-type control mice was evaluated on Coronary blood flow reserve and cardiac function changes after adenosine injection (p=<0.05). In vivo ultrasound assessment in knockout mice confirmed that A2A and A2B receptors primarily mediate adenosine-induced increases in coronary blood flow, while A1, A2A, and A3 receptors modulate overall cardiac function.
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