Hypoxia, endothelium, and purines

Burnstock, Geoffrey

doi:10.1002/ddr.430280320

Cited by 42 publications

(23 citation statements)

References 52 publications

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“…Also, adenosine was not collected in the effluent until long after the hyperemic response occurred, because ADP, after breakdown of released ATP, acts as an inhibitor of 59-nucleotidase breakdown of AMP to adenosine (Ishibashi et al, 1985). Years later, after the seminal studies of Robert Furchgott and others showed that ATP acted on endothelial P2 receptors to release NO, resulting in vasodilation, and it was shown that ATP was released from endothelial cells by hypoxia and increased flow (Bodin et al, 1991;Vials and Burnstock, 1996), Burnstock (1993b) proposed that reactive hyperemia was due to ATP release from endothelial cells during hypoxia acting to release NO. This took place rapidly, and only later, after ATP was broken down by ectoenzymes to adenosine, did coronary vasodilation of vascular smooth muscle via P1 receptors contribute to the hyperemic response.…”

Section: E Coronary Vesselsmentioning

confidence: 99%

“…It was also noted that although reactive hyperemia occurred after about 10 seconds, adenosine did not appear in the perfusate until about 90 seconds. In a counterhypothesis, Burnstock (1993b) proposed that the initial phase of vasodilation after hypoxia was due to ATP released from endothelial cells to cause vasodilation via NO, whereas adenosine (after breakdown of ATP) contributed only to the later stages of reactive hyperemia by acting on P1 receptors on the smooth muscle. The delay in appearance of adenosine in the perfusate was explained by the fact that ADP (after rapid breakdown of ATP) inhibits 59-nucleotidase, the enzyme that mediates breakdown of AMP to adenosine.…”

Section: Ischemiamentioning

confidence: 99%

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Purinergic Signaling and Blood Vessels in Health and Disease

2013

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Section: E Coronary Vesselsmentioning

confidence: 99%

Section: Ischemiamentioning

confidence: 99%

Purinergic Signaling and Blood Vessels in Health and Disease

2013

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“…137 Ischemia and hypoxia lead to a substantial release of ATP from endothelial cells, 64 and adenosine is released from hypoxic heart and skeletal muscle. 138 Adenosine has several cardiovascular protective effects in addition to vasodilation, including the promotion of endothelial cell proliferation and an increased expression of VEGF mRNA. 139 Adenosine also appears to play an important role in preconditioning.…”

Section: Implications For Vascular Diseasementioning

confidence: 99%

Purinergic Signaling and Vascular Cell Proliferation and Death

Burnstock

2002

ATVB

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368

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Abstract-Evidence for the role of purinergic signaling (via P1 and P2Y receptors) in the proliferation of vascular smooth muscle and endothelial cells is reviewed. The involvement of the mitogen-activated protein kinase second-messenger cascade in this action is clearly implicated, although details of the precise intracellular pathways involved still remain to be determined. Synergistic actions of purines and pyrimidines with growth factors occur in promoting cell proliferation. Interaction between purinergic signaling for vascular cell proliferation and cell death mediated by P2X 7 receptors is discussed. There is evidence of the release of ATP from endothelial cells, platelets, and sympathetic nerves as well as from damaged cells in atherosclerosis, hypertension, restenosis, and ischemia; furthermore, there is evidence that vascular smooth muscle and endothelial cells proliferate in these pathological conditions. Thus, the involvement of ATP and its breakdown product, adenosine, is implicated; it is hoped that with the development of selective P1 (A 2 ) and P2Y receptor agonists and antagonists, new therapeutic strategies will be explored.

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“…Although reactive hyperemia occurs ≈10 seconds after resumption of blood flow, adenosine does not appear in the perfusate until ≈90 seconds later because ADP, the first breakdown product, inhibits ecto-5′nucleotidase (CD73). Burnstock 22 claimed that ATP, released during hypoxia from endothelial cells promoting the production of nitric oxide (NO), is the compound initially responsible for reactive hyperemia and that adenosine, after breakdown of ATP, acts later as a dilator via A 1 receptors on smooth muscle.…”

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confidence: 99%

Purinergic Signaling in the Cardiovascular System

Burnstock

2017

Circulation Research

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339

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Abstract:There is nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory-motor nerves, as well as in intracardiac neurons. Centers in the brain control heart activities and vagal cardiovascular reflexes involve purines. Adenine nucleotides and nucleosides act on purinoceptors on cardiomyocytes, AV and SA nodes, cardiac fibroblasts, and coronary blood vessels. Vascular tone is controlled by a dual mechanism. ATP, released from perivascular sympathetic nerves, causes vasoconstriction largely via P2X1 receptors. Endothelial cells release ATP in response to changes in blood flow (via shear stress) or hypoxia, to act on P2 receptors on endothelial cells to produce nitric oxide, endothelium-derived hyperpolarizing factor, or prostaglandins to cause vasodilation. ATP is also released from sensory-motor nerves during antidromic reflex activity, to produce relaxation of some blood vessels. Purinergic signaling is involved in the physiology of erythrocytes, platelets, and leukocytes. ATP is released from erythrocytes and platelets, and purinoceptors and ectonucleotidases are expressed by these cells. P1, P2Y 1 , P2Y 12 , and P2X1 receptors are expressed on platelets, which mediate platelet aggregation and shape change. Long-term (trophic) actions of purine and pyrimidine nucleosides and nucleotides promote migration and proliferation of vascular smooth muscle and endothelial cells via P1 and P2Y receptors during angiogenesis, vessel remodeling during restenosis after angioplasty and atherosclerosis. The involvement of purinergic signaling in cardiovascular pathophysiology and its therapeutic potential are discussed, including heart failure, infarction, arrhythmias, syncope, cardiomyopathy, angina, heart transplantation and coronary bypass grafts, coronary artery disease, diabetic cardiomyopathy, hypertension, ischemia, thrombosis, diabetes mellitus, and migraine. (Circ Res. 2017;120:207-228.

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Hypoxia, endothelium, and purines

Cited by 42 publications

References 52 publications

Purinergic Signaling and Blood Vessels in Health and Disease

Purinergic Signaling and Blood Vessels in Health and Disease

Purinergic Signaling and Vascular Cell Proliferation and Death

Purinergic Signaling in the Cardiovascular System

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