Sympathetic innervation of the kidney in health and disease: Emphasis on the role of purinergic cotransmission

Burnstock, Geoffrey; Loesch, Andrzej

doi:10.1016/j.autneu.2016.05.007

Cited by 22 publications

(17 citation statements)

References 144 publications

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“…Reviews are available ( Burnstock et al, 2014a ; Menzies et al, 2017 ; Oyarzun et al, 2017 ), including one that focuses on the roles played by ATP released as a cotransmitter from sympathetic nerves in renal diseases ( Burnstock and Loesch, 2017 ).…”

Section: Diseases Of the Kidneymentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

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Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

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Section: Diseases Of the Kidneymentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

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“…Increased renal sympathetic nerve activity (RSNA), and hence increased noradrenaline release, decrease renal blood flow and increase sodium retention and renin release 80,81 .…”

Section: Neural Circuits In the Kidneymentioning

confidence: 99%

Targeting neural reflex circuits in immunity to treat kidney disease

2017

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Neural pathways regulate immunity and inflammation via the inflammatory reflex and specific molecular targets can be modulated by stimulating neurons. Neuroimmunomodulation by nonpharmacological methods is emerging as a novel therapeutic strategy for inflammatory diseases, including kidney diseases and hypertension. Electrical stimulation of vagus neurons or treatment with pulsed ultrasound activates the cholinergic anti-inflammatory pathway (CAP) and protects mice from acute kidney injury (AKI). Direct innervation of the kidney, by afferent and efferent neurons, might have a role in modulating and responding to inflammation in various diseases, either locally or by providing feedback to regions of the central nervous system that are important in the inflammatory reflex pathway. Increased sympathetic drive to the kidney has a role in the pathogenesis of hypertension, and selective modulation of neuroimmune interactions in the kidney could potentially be more effective for lowering blood pressure and treating inflammatory kidney diseases than renal denervation. Use of optogenetic tools for selective stimulation of specific neurons has enabled the identification of neural circuits in the brain that modulate kidney function via activation of the CAP. In this Review we discuss evidence for a role of neural circuits in the control of renal inflammation as well as the therapeutic potential of targeting these circuits in the settings of AKI, kidney fibrosis and hypertension.

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“…For example, renal sympathetic nerves, which are chronically activated in various forms of hypertension, influence renin release, tubuloglomerular feedback and glomerular filtration rate and modulate sodium, water and ion reabsorption (DiBona & Kopp, ; Johns et al . ; Burnstock & Loesch, ). Numerous mechanisms in the kidney that can lead to ER stress (e.g.…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic reticulum stress in the pathogenesis of hypertension

Young

2017

Experimental Physiology

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What is the topic of this review? This review highlights the emerging role of disruptions in endoplasmic reticulum (ER) function, namely ER stress, as a contributor to hypertension. What advances does it highlight? This review presents an integrative view of ER stress in cardiovascular control systems, including systems within the brain, kidney and peripheral vasculature, as related to development of hypertension. The endoplasmic reticulum (ER) is a cellular organelle specialized in the synthesis, folding, assembly and modification of proteins. In situations of increased protein demand, complex signalling pathways, termed the unfolded protein response, influence a series of cellular feedback loops to control ER function strictly. Although this is initially a compensatory attempt to maintain cellular homeostasis, chronic activation of the unfolded protein response, known as ER stress, leads to sustained changes in cellular function. A growing body of literature points to ER stress in diverse cardioregulatory systems, including the brain, kidney and vasculature, as central to the development of hypertension. Here, these recent findings from essential and obesity-related forms of hypertension are highlighted in an integrative manner, with discussion of the potential upstream causes and downstream consequences of ER stress. Given that hypertension is a leading medical and socio-economic global challenge, emerging findings suggest that targeting ER stress might represent a viable strategy for the treatment of hypertensive disease.

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Sympathetic innervation of the kidney in health and disease: Emphasis on the role of purinergic cotransmission

Cited by 22 publications

References 144 publications

Purinergic Signalling: Therapeutic Developments

Purinergic Signalling: Therapeutic Developments

Targeting neural reflex circuits in immunity to treat kidney disease

Endoplasmic reticulum stress in the pathogenesis of hypertension

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