Effects of aging and ischemia on adenosine receptor transcription in mouse myocardium

Ashton, Kevin J.; Nilsson, Ulrika Wilhelmina; Willems, Laura; Holmgren, Kirsty; Headrick, John P.

doi:10.1016/j.bbrc.2003.10.127

Cited by 29 publications

(29 citation statements)

References 20 publications

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“…Second, what is intriguing is that this finding is very similar to the adaptive mechanism found in pathophysiological condition, such as cardiac ischemia. Previous studies from our group and others found that A 2B AR was up-regulated in ischemic mouse hearts [16,17]. A 2B AR has recently been shown to have cardio-protective properties [18,19] However, A 2B AR-mediated CF regulation under ischemic conditions has not been studied.…”

Section: Discussionmentioning

confidence: 92%

“…It has been speculated that under pathological conditions, such as ischemia, A 2B AR may be up-regulated to compensate for the down-regulation of A 2A AR-mediated responses. Indeed, an up-regulation of A 2B AR gene expression has been found in ischemic mouse hearts [16,17]. We suspect that this kind of adaptive mechanism may also happen in the knockout animals.…”

Section: Introductionmentioning

confidence: 87%

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Up-regulation of A2B adenosine receptor in A2A adenosine receptor knockout mouse coronary artery

Teng¹,

Ledent²,

Mustafa³

2008

Journal of Molecular and Cellular Cardiology

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In this study, we looked into possible compensatory changes of other adenosine receptors (AR) in A 2A genetic knockout mice (A2AKO) as well as the functional role of nitric oxide (NO) in A 2A ARmediated vasodilation. Gene expression of ARs from coronary arteries of A 2A AR wild type mice (A2AWT) and A2AKO were studied using real time-PCR. Functional studies were carried out in isolated heart and isolated coronary artery preparations. A 2B AR was found to be 4.5 fold higher in A2AKO than in A2AWT, while A 2A AR expression was absent in A2AKO. There was no difference in A 1 and A 3 ARs between WT and KO animals. The concentration-relaxation curve for adenosine-5′-N-ethylcarboxamide (NECA, non-selective AR agonist) in isolated coronary arterial rings in A2AKO was shifted to the left when compared to A2AWT. The concentration-response curve for A 2B selective agonist (Bay 60-6583) was also shifted to the left in A2AKO hearts. L-NAME, a nonspecific NO synthase inhibitor, did not affect baseline coronary flow (CF) until the concentration reached 10 µM in A 2A WT (76.32 ± 11.35% from baseline, n=5). In A 2A KO, the CF decreased significantly by L-NAME only at a higher concentration (100 µM, 93.32 ± 5.8% from baseline, n=5). L-NMA (1 µM, n=4), another non-specific NO synthase inhibitor, also demonstrated similar results in decreasing CF (59.66±3.23% from baseline in A2AWT, while 81.76±8.91% in A2AKO). It was further demonstrated that the increase in CF by 100 µM NECA was significantly blunted with 10 µM L-NAME (377.08 ± 25.23% to 305.41 ± 30.73%, n=9) in A 2A WT but not in A 2A KO (153.66 ± 22.7% to 143.88 ± 36.65%, n=5). Similar results were also found using 50 nM of CGS-21680 instead of NECA in A 2A WT (346±22.85 to 277±31.39, n=6). No change in CF to CGS-21680 was noted in A 2A AKO. Our data demonstrate, for the first time, that coronary A 2B AR was up-regulated in mice deficient in A 2A AR. We also provide direct evidence supporting a role for NO in A 2A AR-mediated coronary vasodilation. The data further support the role for A 2A AR in the regulation of basal coronary tone through the release of NO.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 87%

Up-regulation of A2B adenosine receptor in A2A adenosine receptor knockout mouse coronary artery

Teng¹,

Ledent²,

Mustafa³

2008

Journal of Molecular and Cellular Cardiology

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“…There is decreased adenosine protection in reperfusion injury in aging rats (Gao et al, 2000). Reduced A 3 receptor transcription may contribute to improved ischemia tolerance in aged hearts (Ashton et al, 2003). Low-dose adenosine infusion reduced the ischemic burden and improved left ventricular regional systolic function in the ischemic walls of patients with exercise-induced myocardial ischemia (Sadigh et al, 2009).…”

Section: Ischemiamentioning

confidence: 99%

Purinergic Signaling and Blood Vessels in Health and Disease

2013

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“…In a later study, it was shown that improved resistance of the heart to ischaemic damage can be achieved by increasing the expression of A3R, without detrimental side effects on heart rate or systolic function [530]. Reduced A3R transcription may contribute to improved ischaemia tolerance in aged hearts [531]. Reduction in post-ischaemic inflammation and infarct size was achieved by perfusion of the canine myocardium with a selective A2AR agonist [532].…”

Section: Ischaemiamentioning

confidence: 99%

Cardiac purinergic signalling in health and disease

Burnstock

Pelleg

2014

Purinergic Signalling

119

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This review is a historical account about purinergic signalling in the heart, for readers to see how ideas and understanding have changed as new experimental results were published. Initially, the focus is on the nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory nerves, as well as in intracardiac neurons. Control of the heart by centers in the brain and vagal cardiovascular reflexes involving purines are also discussed. The actions of adenine nucleotides and nucleosides on cardiomyocytes, atrioventricular and sinoatrial nodes, cardiac fibroblasts, and coronary blood vessels are described. Cardiac release and degradation of ATP are also described. Finally, the involvement of purinergic signalling and its therapeutic potential in cardiac pathophysiology is reviewed, including acute and chronic heart failure, ischemia, infarction, arrhythmias, cardiomyopathy, syncope, hypertrophy, coronary artery disease, angina, diabetic cardiomyopathy, as well as heart transplantation and coronary bypass grafts.

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Effects of aging and ischemia on adenosine receptor transcription in mouse myocardium

Cited by 29 publications

References 20 publications

Up-regulation of A2B adenosine receptor in A2A adenosine receptor knockout mouse coronary artery

Up-regulation of A2B adenosine receptor in A2A adenosine receptor knockout mouse coronary artery

Purinergic Signaling and Blood Vessels in Health and Disease

Cardiac purinergic signalling in health and disease

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