ArticleAmerican journal of physiology. Heart and circulatory physiology2013
Interactions between A(2A) adenosine receptors, hydrogen peroxide, and KATP channels in coronary reactive hyperemia.
Article in American journal of physiology. Heart and circulatory physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- The Role of Adenosine A1 and A2a Receptors in Cerebral Blood Vessel Reactivity of Sprague Dawley Rats Exposed to Hyperbaric Oxygenation.Molecules (Basel, Switzerland) · 2025Article
- A2AR-mediated lymphangiogenesis via VEGFR2 signaling prevents salt-sensitive hypertension.European heart journal · 2023Article
- Basal NAD(H) redox state permits hydrogen peroxide-induced mesenteric artery dilatation.The Journal of physiology · 2023Article
- Inhibition of Endoplasmic Reticulum Stress Improves Acetylcholine-Mediated Relaxation in the Aorta of Type-2 Diabetic Rats.Molecules (Basel, Switzerland) · 2022Article
- Adenosine and adenosine receptor-mediated action in coronary microcirculation.Basic research in cardiology · 2021Review
- Alteration of purinergic signaling in diabetes: Focus on vascular function.Journal of molecular and cellular cardiology · 2020Review
- Activation of adenosine AJournal of pharmacological sciences · 2019Article
- Enhanced AEuropean journal of pharmacology · 2019Article
- Kv1.3 channels facilitate the connection between metabolism and blood flow in the heart.Microcirculation (New York, N.Y. : 1994) · 2017Review
- Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles.Comprehensive Physiology · 2017Review
- Inosine attenuates spontaneous activity in the rat neurogenic bladder through an AScientific reports · 2017Article
- Potassium Channels in Regulation of Vascular Smooth Muscle Contraction and Growth.Advances in pharmacology (San Diego, Calif.) · 2017Review
- Deletion of soluble epoxide hydrolase enhances coronary reactive hyperemia in isolated mouse heart: role of oxylipins and PPARγ.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Article
- Adenosine relaxation in isolated rat aortic rings and possible roles of smooth muscle Kv channels, KATP channels and A2a receptors.BMC pharmacology & toxicology · 2016Article
- Effect of Soluble Epoxide Hydrolase on the Modulation of Coronary Reactive Hyperemia: Role of Oxylipins and PPARγ.PloS one · 2016Article
- Enhanced A2A adenosine receptor-mediated increase in coronary flow in type I diabetic mice.Journal of molecular and cellular cardiology · 2016Article
- Sex Difference in Coronary Endothelial Dysfunction in Apolipoprotein E Knockout Mouse: Role of NO and A2A Adenosine Receptor.Microcirculation (New York, N.Y. : 1994) · 2015Article
- Angiotensin II stimulation alters vasomotor response to adenosine in mouse mesenteric artery: role for A1 and A2B adenosine receptors.British journal of pharmacology · 2015Article
- Involvement of NADPH oxidase in A2A adenosine receptor-mediated increase in coronary flow in isolated mouse hearts.Purinergic signalling · 2015Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Myocardial metabolites such as adenosine mediate reactive hyperemia, in part, by activating ATP-dependent K(+) (K(ATP)) channels in coronary smooth muscle. In this study, we investigated the role of adenosine A(2A) and A(2B) receptors and their signaling mechanisms in reactive hyperemia. We hypothesized that coronary reactive hyperemia involves A(2A) receptors, hydrogen peroxide (H(2)O(2)), and KATP channels. We used A(2A) and A(2B) knockout (KO) and A(2A/2B) double KO (DKO) mouse hearts for Langendorff experiments. Flow debt for a 15-s occlusion was repaid 128 ± 8% in hearts from wild-type (WT) mice; this was reduced in hearts from A(2A) KO and A(2A)/(2B) DKO mice (98 ± 9 and 105 ± 6%; P < 0.05), but not A(2B) KO mice (123 ± 13%). Patch-clamp experiments demonstrated that adenosine activated glibenclamide-sensitive KATP current in smooth muscle cells from WT and A(2B) KO mice (90 ± 23% of WT) but not A(2A) KO or A(2A)/A(2B) DKO mice (30 ± 4 and 35 ± 8% of WT; P < 0.05). Additionally, H(2)O(2) activated KATP current in smooth muscle cells (358 ± 99%; P < 0.05). Catalase, an enzyme that breaks down H(2)O(2), attenuated adenosine-induced coronary vasodilation, reducing the percent increase in flow from 284 ± 53 to 89 ± 13% (P < 0.05). Catalase reduced the repayment of flow debt in hearts from WT mice (84 ± 9%; P < 0.05) but had no effect on the already diminished repayment in hearts from A(2A) KO mice (98 ± 7%). Our findings suggest that adenosine A(2A) receptors are coupled to smooth muscle KATP channels in reactive hyperemia via the production of H(2)O(2) as a signaling intermediate.
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