Julian F R Paton

University of Bristol, Bristol, England, United Kingdom

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Publications (329)1218.9 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The polyamines spermidine and spermine are small cations present in all living cells. In the brain, these cations are particularly abundant in the neurons of the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus, which synthesise the neuropeptide hormones arginine vasopressin (AVP) and oxytocin (OT). We recently reported increased mRNA expression of antizyme inhibitor 1 (Azin1), an important regulator of polyamine synthesis, in rat SON and PVN as a consequence of 3 days of dehydration (DH). Here, we show that Azin1 protein is highly expressed in both AVP and OT positive magnocellular neurons of the SON and PVN, together with antizyme 1 (AZ1), ornithine decarboxylase (ODC) and polyamines. Azin1 mRNA expression increased in the SON and PVN as a consequence of DH, salt loading (SL) and by acute hypertonic stress. In organotypic hypothalamic cultures, addition of the irreversible ODC inhibitor DL-2-(Difluoromethyl)-ornithine hydrochloride (DFMO) significantly increased the abundance of heteronuclear AVP (hnAVP), but not hnOT. To identify the function of Azin1 in vivo, lentiviral vectors that either over-express or knockdown Azin1 were stereotaxically delivered into the SON and/or PVN. Azin1 shRNA delivery resulted in decreased plasma osmolality and had a significant effect on food intake. The expression of AVP mRNA was also significantly increased in the SON by Azin1 shRNA. In contrast, Azin1 overexpression in the SON decreased AVP mRNA expression. We have therefore identified Azin1, and hence by inference polyamines, as novel regulators of the expression of the AVP gene.
    Endocrinology 05/2015; DOI:10.1210/en.2015-1074 · 4.64 Impact Factor
  • PLoS ONE 04/2015; 10(4):e0124956. DOI:10.1371/journal.pone.0124956 · 3.53 Impact Factor
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    ABSTRACT: A great deal of basic and applied physiology and pharmacology in sensory and autonomic neuroscience has teased apart mechanisms that drive normal perception of mechanical, thermal and chemical signals and convey them to CNS, the distinction of fiber types and receptors and channels that mediate them, and how they may become dysfunctional or maladaptive in disease. Likewise, regulation of efferent autonomic traffic to control organ reflexes has been well studied. In both afferent and efferent limbs, a wide array of potential therapeutic mechanisms has surfaced, some of which have progressed into clinic, if not full regrastration. One conversation that has been less well progressed relates to how the afferent limb and its sensitization shapes the efferent outputs, and where modulation may offer new therapeutic avenues, especially for poorly addressed and common signs and symptoms of disease. Therapeutics for CV disease (HF, hypertension), respiratory disease (asthma, COPD), urological disease (OAB), GI disease (IBS), and inter alia, have largely focused on the efferent control of effector cells to modulate movement, contraction and secretion; medicinal needs remain with limits to efficacy, AEs and treatment resistance being common. We now must turn, in the quest for improved therapeutics, to understand how sensation from these organs becomes maladapted and sensitized in disease, and what opportunities may arise for improved therapeutics given the abundance of targets, many pharmacologically untapped, on the afferent side. One might look at the treatment resistant hypertension and the emerging benefit of renal denervation; or urinary bladder overactivity / neurogenic bladder and the emergence of neuromodulation, capsaicin instillation or botox injections to attenuate sensitized reflexes, as examples of merely the start of such progress. This review examines this topic more deeply, as applies to four major organ systems all sharing a great need from unsatisfied patients. Copyright © 2015 Elsevier B.V. All rights reserved.
    Autonomic neuroscience: basic & clinical 04/2015; DOI:10.1016/j.autneu.2015.04.005 · 1.37 Impact Factor
  • Davi J A Moraes, Benedito H Machado, Julian F R Paton
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    ABSTRACT: Why sympathetic activity raises in neurogenic hypertension remains unknown. It has been postulated that changes in the electrical excitability of medullary pre-sympathetic neurones are the main causal mechanism for the development of sympathetic over activity in experimental hypertension. Herein, we review recent data suggesting that enhanced sympathetic activity in neurogenic hypertension is, at least in part, dependent on alterations in the electrical excitability of medullary respiratory neurones and their central modulation of sympatho-excitatory networks. We also present results showing a critical role for carotid body tonicity in the etiology of enhanced central respiratory modulation of sympathetic activity in neurogenic hypertension. We propose a novel hypothesis of respiratory neurone channelopathy induced by carotid body over activity in neurogenic hypertension that may contribute to sympathetic excess. Moreover, our data support the notion of targeting the carotid body as a potential novel therapeutic approach for reducing sympathetic vasomotor tone in neurogenic hypertension. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    The Journal of Physiology 04/2015; DOI:10.1113/JP270423 · 4.54 Impact Factor
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    ABSTRACT: The Na-K-2Cl cotransporter 2 (NKCC2) was thought to be kidney specific. Here we show expression in the brain hypothalamo-neurohypophyseal system (HNS), wherein upregulation follows osmotic stress. The HNS controls osmotic stability through the synthesis and release of the neuropeptide hormone, arginine vasopressin (AVP). AVP travels through the bloodstream to the kidney, where it promotes water conservation. Knockdown of HNS NKCC2 elicited profound effects on fluid balance following ingestion of a high-salt solution-rats produced significantly more urine, concomitant with increases in fluid intake and plasma osmolality. Since NKCC2 is the molecular target of the loop diuretics bumetanide and furosemide, we asked about their effects on HNS function following disturbed water balance. Dehydration-evoked GABA-mediated excitation of AVP neurons was reversed by bumetanide, and furosemide blocked AVP release, both in vivo and in hypothalamic explants. Thus, NKCC2-dependent brain mechanisms that regulate osmotic stability are disrupted by loop diuretics in rats. Copyright © 2015 the authors 0270-6474/15/355144-12$15.00/0.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 04/2015; 35(13):5144-55. DOI:10.1523/JNEUROSCI.4121-14.2015 · 6.75 Impact Factor
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    ABSTRACT: Systemic arterial hypertension has been previously suggested to develop as a compensatory condition when central nervous perfusion/oxygenation is compromised. Principal sympathoexcitatory C1 neurons of the rostral ventrolateral medulla oblongata (whose activation increases sympathetic drive and the arterial blood pressure) are highly sensitive to hypoxia, but the mechanisms of this O2 sensitivity remain unknown. Here, we investigated potential mechanisms linking brainstem hypoxia and high systemic arterial blood pressure in the spontaneously hypertensive rat. Brainstem parenchymal PO2 in the spontaneously hypertensive rat was found to be ≈15 mm Hg lower than in the normotensive Wistar rat at the same level of arterial oxygenation and systemic arterial blood pressure. Hypoxia-induced activation of rostral ventrolateral medulla oblongata neurons was suppressed in the presence of either an ATP receptor antagonist MRS2179 or a glycogenolysis inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol, suggesting that sensitivity of these neurons to low PO2 is mediated by actions of extracellular ATP and lactate. Brainstem hypoxia triggers release of lactate and ATP which produce excitation of C1 neurons in vitro and increases sympathetic nerve activity and arterial blood pressure in vivo. Facilitated breakdown of extracellular ATP in the rostral ventrolateral medulla oblongata by virally-driven overexpression of a potent ectonucleotidase transmembrane prostatic acid phosphatase results in a significant reduction in the arterial blood pressure in the spontaneously hypertensive rats (but not in normotensive animals). These results suggest that in the spontaneously hypertensive rat, lower PO2 of brainstem parenchyma may be associated with higher levels of ambient ATP and l-lactate within the presympathetic circuits, leading to increased central sympathetic drive and concomitant sustained increases in systemic arterial blood pressure.
    Hypertension 04/2015; 65(4):775-83. · 7.63 Impact Factor
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    ABSTRACT: This paper explores the influence of burst properties of the sympathetic nervous system on arterial contractility. Specifically, a mathematical model is constructed of the pathway from action potential generation in a sympathetic postganglionic neurone to contraction of an arterial smooth muscle cell. The differential equation model is a synthesis of models of the individual physiological processes, and is shown to be consistent with physiological data. The model is found to be unresponsive to tonic (regular) stimulation at typical frequencies recorded in sympathetic efferents. However, when stimulated at the same average frequency, but with repetitive respiratory-modulated burst patterns, it produces marked contractions. Moreover, the contractile force produced is found to be highly dependent on the number of spikes in each burst. In particular, when the model is driven by preganglionic spike trains recorded from wild-type and spontaneously hypertensive rats (which have increased spiking during each burst) the contractile force was found to be 10-fold greater in the hypertensive case. An explanation is provided in terms of the summative increased release of noradrenaline. Furthermore, the results suggest the marked effect that hypertensive spike trains had on smooth muscle cell tone can provide a significant contribution to the pathology of hypertension. Copyright © 2015. Published by Elsevier Ltd.
    Journal of Theoretical Biology 02/2015; 149. DOI:10.1016/j.jtbi.2015.01.037 · 2.30 Impact Factor
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    ABSTRACT: The idea that the sympathetic nervous system (SNS) plays an important role in the initiation or maintenance of hypertension has been considered for decades. In fact, in the 1940 s, surgical lumbar sympathectomy and splanchnic resection were employed for the treatment of hypertension (Smithwick, 1940; Grimson, 1941).This article is protected by copyright. All rights reserved
    Experimental physiology 01/2015; 100(5). DOI:10.1113/expphysiol.2014.079855 · 2.87 Impact Factor
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    ABSTRACT: Salt loading (SL) and water deprivation (WD) are experimental challenges that are often used to study the osmotic circuitry of the brain. Central to this circuit is the supraoptic nucleus (SON) of the hypothalamus, which is responsible for the biosynthesis of the hormones, vasopressin (AVP) and oxytocin (OXT), and their transport to terminals that reside in the posterior lobe of the pituitary. Upon osmotic challenge evoked by a change in blood volume or osmolality, the SON undergoes a function related plasticity that creates an environment that allows for an appropriate hormone response. Here, we have described the impact of SL and WD compared to euhydrated (EU) controls in terms of drinking and eating behaviour, body weight and recorded physiological data including circulating hormone data and plasma and urine osmolality. We have also used microarrays to profile the transcriptome of the SON following SL and re-mined data from the SON that describes the transcriptome response to WD. From a list of 2,783 commonly regulated transcripts, we selected 20 genes for validation by qPCR. All of the 9 genes that have already been described as expressed or regulated in the SON by osmotic stimuli were confirmed in our models. Of the 11 novel genes, 7 were successfully validated while 4 were false discoveries. Copyright © 2014, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology.
    AJP Regulatory Integrative and Comparative Physiology 01/2015; 308(7):ajpregu.00444.2014. DOI:10.1152/ajpregu.00444.2014 · 3.53 Impact Factor
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    18th Annual SCMR; 01/2015
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    ABSTRACT: Objectives Rheumatoid arthritis (RA) is a chronic inflammatory condition with increased all-cause and cardiovascular mortality. Accumulating evidence indicates that the immune and autonomic nervous systems (ANS) are major contributors to the pathogenesis of cardiovascular disease. We performed the first systematic literature review to determine the prevalence and nature of ANS dysfunction in RA and whether there is a causal relationship between inflammation and ANS function. Methods Electronic databases (Medline, Central and Cochrane Library) were searched for studies of RA patients where autonomic function was assessed. Results Forty studies in total were included. ANS function was assessed by clinical cardiovascular reflex tests (CCTs)(n=18), heart rate variability (HRV)(n=15), catecholamines (n=5), biomarkers of sympathetic activity (n=5), sympathetic skin responses (n=5), cardiac baroreflex sensitivity (cBRS) (n=2) and pupillary light reflexes (n=2). 9 small studies reported a ~60% (median, range 20-86%) prevalence of ANS dysfunction (defined by abnormal CCTs) in RA. 73% of studies (n=27/37) reported at least one abnormality in ANS function: parasympathetic dysfunction (n=20/26, 77%), sympathetic dysfunction (n=16/30, 53%) or reduced cBRS (n=1/2, 50%). An association between increased inflammation and ANS dysfunction was found (n=7/19, 37%) although causal relationships could not be elucidated from the studies available to date. Conclusions ANS dysfunction is prevalent in ~60% of RA patients. The main pattern of dysfunction is impairment of cardiovascular reflexes and altered HRV indicative of reduced cardiac parasympathetic (strong evidence) and elevated cardiac sympathetic activity (limited evidence). The literature to date is underpowered to determine causal relationships between inflammation and ANS dysfunction in RA.
    Seminars in Arthritis and Rheumatism 12/2014; 44(3). DOI:10.1016/j.semarthrit.2014.06.003 · 3.63 Impact Factor
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    ABSTRACT: Cardiac rhythm management devices provide therapies for both arrhythmias and resynchronization but not heart failure, which affects millions of patients worldwide. This paper reviews recent advances in biophysics and mathematical engineering that provide a novel technological platform for addressing heart disease and enabling beat-to-beat adaptation of cardiac pacing in response to physiological feedback. The technology consists of silicon hardware central pattern generators (hCPG) that may be trained to emulate accurately the dynamical response of biological central pattern generators (bCPG). We discuss the limitations of present CPGs and appraise the advantages of analogue over digital circuits for application in bioelectronic medicine. To test the system, we have focused on the cardio-respiratory oscillators in the medulla oblongata that modulate heart rate in phase with respiration to induce respiratory sinus arrhythmia (RSA). We describe here a novel, scalable hCPG comprising physiologically realistic (Hodgkin-Huxley type) neurones and synapses. Our hCPG comprises two neurones that antagonise each other to provide rhythmic motor drive to the vagus nerve to slow the heart. We show how recent advances in modelling allow the motor output to adapt to physiological feedback such as respiration. In rats, we report on the restoration of RSA using an hCPG that receives diaphragmatic electromyography input and use it to stimulate the vagus nerve at specific time points of the respiratory cycle to slow the heart rate. We have validated the adaptation of stimulation to alterations in respiratory rate. We demonstrate that the hCPG is tuneable in terms of the depth and timing of the RSA relative to respiratory phase. These pioneering studies will now permit an analysis of the physiological role of RSA as well as its any potential therapeutic use in cardiac disease.This article is protected by copyright. All rights reserved
    The Journal of Physiology 11/2014; 593(4). DOI:10.1113/jphysiol.2014.282723 · 4.54 Impact Factor
  • Ana Paula Abdala, Julian F. R. Paton, Jeffrey C. Smith
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    ABSTRACT: Pharmacological and mathematical modelling studies support the view that synaptic inhibition in mammalian brainstem respiratory circuits is essential for generating normal and stable breathing movements. GABAergic and glycinergic neurones are known components of these circuits but their precise functional roles have not been established, especially within key microcircuits of the respiratory pre-Bötzinger (pre-BötC) and Bötzinger (BötC) complexes involved in phasic control of respiratory pump and airway muscles. Here, we review briefly current concepts of relevant complexities of inhibitory synapses and the importance of synaptic inhibition in the operation of these microcircuits. We highlight results and limitations of classical pharmacological studies that have suggested critical functions of synaptic inhibition. We then explore the potential opportunities for optogenetic strategies that represent a promising new approach for interrogating function of inhibitory circuits, including a hypothetical wish list for optogenetic approaches to allow expedient application of this technology. We conclude that recent technical advances in optogenetics should provide a means to understand the role of functionally select and regionally confined subsets of inhibitory neurones in key respiratory circuits such as those in the pre-BötC and BötC.This article is protected by copyright. All rights reserved
    The Journal of Physiology 11/2014; DOI:10.1113/jphysiol.2014.280610 · 4.54 Impact Factor
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    ABSTRACT: Hypertension is a leading risk factor for the development of several cardiovascular diseases. As the global prevalence of hypertension increases, so too has the recognition of resistant hypertension. Whilst figures vary, the proportion of hypertensive patients that are resistant to multiple drug therapies have been reported to be as high as 16.4 %. Resistant hypertension is typically associated with elevated sympathetic activity and abnormal homeostatic reflex control and is termed neurogenic hypertension because of its presumed central autonomic nervous system origin. This resistance to conventional pharmacological treatment has stimulated a plethora of medical devices to be investigated for use in hypertension, with varying degrees of success. In this review, we discuss a new therapy for drug-resistant hypertension, deep brain stimulation. The utility of deep brain stimulation in resistant hypertension was first discovered in patients with concurrent neuropathic pain, where it lowered blood pressure and improved baroreflex sensitivity. The most promising central target for stimulation is the ventrolateral periaqueductal gray, which has been well characterised in animal studies as a control centre for autonomic outflow. In this review, we will discuss the promise and potential mechanisms of deep brain stimulation in the treatment of severe, resistant hypertension.
    Current Hypertension Reports 11/2014; 16(11):493. DOI:10.1007/s11906-014-0493-1 · 3.90 Impact Factor
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    ABSTRACT: Background It is well established that sympathetic nervous system is responsible for the onset, development and maintenance of neurogenic hypertension. The rostroventrolateral medulla (RVLM) and medullo-cervical pressor area (MCPA) are important central sympathoexcitatory regions which role on neurogenic hypertension remains unknown. Objective To establish RVLM and MCPA roles in the long-term regulation of blood pressure by depressing their neurons activity through the over-expression of hKir2.1-potassium channel in conscious spontaneously hypertensive rats (SHR). Methods In SHR, a lentiviral vector LVV-hKir2.1 was microinjected into RVLM or MCPA areas. A sham group was injected with LVV-eGFP. Blood pressure (BP), heart rate (HR) were continuously monitored for 75 days. Baroreflex and chemoreflex function were evaluated. Baroreflex gain, chemoreflex sensitivity, BP and HR variability were calculated. Results LVV-hKir2.1 expression in RVLM, but not in MCPA, produced a significant time-dependent decrease in systolic, diastolic,mean-BP and LF of systolicBP at 60-days post-injection. No significant changes were seen in LVV-eGFP RVLM injected SHR. Conclusion Data show that chronic expression of Kir2.1 in the RVLM of conscious SHR caused a marked and sustained decrease in BP without changes in the baro- and peripheral chemoreceptor reflex evoked responses. This decrease was mostly due to a reduction in sympathetic output revealed indirectly by a decrease in the power density of the SBP- LF band. Our data are amongst the first to demonstrate the role of the RVLM in maintaining BP levels in hypertension in conscious SHR. We suggest that a decrease in RVLM neuronal activity is an effective anti-hypertensive treatment strategy.
    Autonomic Neuroscience 09/2014; DOI:10.1016/j.autneu.2014.09.002 · 1.37 Impact Factor
  • The Journal of Physiology 09/2014; 592(18). DOI:10.1113/jphysiol.2013.268227 · 4.54 Impact Factor
  • The Journal of Physiology 09/2014; 592(18). DOI:10.1113/jphysiol.2014.279737 · 4.54 Impact Factor
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    ABSTRACT: Salt appetite, the primordial instinct to favorably ingest salty substances, represents a vital evolutionary important drive to successfully maintain body fluid and electrolyte homeostasis. This innate instinct was shown here in Sprague-Dawley rats by increased ingestion of isotonic saline (IS) over water in fluid intake tests. However, this appetitive stimulus was fundamentally transformed into a powerfully aversive one by increasing the salt content of drinking fluid from IS to hypertonic saline (2% w/v NaCl, HS) in intake tests. Rats ingested HS similar to IS when given no choice in one-bottle tests and previous studies have indicated that this may modify salt appetite. We thus investigated if a single 24 h experience of ingesting IS or HS, dehydration (DH) or 4% high salt food (HSD) altered salt preference. Here we show that 24 h of ingesting IS and HS solutions, but not DH or HSD, robustly transformed salt appetite in rats when tested 7 days and 35 days later. Using two-bottle tests rats previously exposed to IS preferred neither IS or water, whereas rats exposed to HS showed aversion to IS. Responses to sweet solutions (1% sucrose) were not different in two-bottle tests with water, suggesting that salt was the primary aversive taste pathway recruited in this model. Inducing thirst by subcutaneous administration of angiotensin II did not overcome this salt aversion. We hypothesised that this behavior results from altered gene expression in brain structures important in thirst and salt appetite. Thus we also report here lasting changes in mRNAs for markers of neuronal activity, peptide hormones and neuronal plasticity in supraoptic and paraventricular nuclei of the hypothalamus following rehydration after both DH and HS. These results indicate that a single experience of drinking HS is a memorable one, with long-term changes in gene expression accompanying this aversion to salty solutions.
    PLoS ONE 08/2014; 9(8):e104802. DOI:10.1371/journal.pone.0104802 · 3.53 Impact Factor
  • Alona Ben-Tal, Sophie S Shamailov, Julian F R Paton
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    ABSTRACT: A minimal model for the neural control of heart rate (HR) has been developed with the aim of better understanding respiratory sinus arrhythmia (RSA) - a modulation of HR at the frequency of breathing. This model consists of two differential equations and is integrated into a previously-published model of gas exchange. The heart period is assumed to be affected primarily by the parasympathetic signal, with the sympathetic signal taken as a parameter in the model. We include the baroreflex, mechanical stretch-receptor feedback from the lungs, and central modulation of the cardiac vagal tone by the respiratory drive. Our model mimics a range of experimental observations and provides several new insights. Most notably, the model mimics the growth in the amplitude of RSA with decreasing respiratory frequency up to 7 breaths per minute (for humans). Our model then mimics the decrease in the amplitude of RSA at frequencies below 7 breaths per minute and predicts that this decrease is due to the baroreflex (we show this both numerically and analytically with a linear baroreflex). Another new prediction of the model is that the gating of the baroreflex leads to the dependency of RSA on mean vagal tone. The new model was also used to test two previously-suggested hypotheses regarding the physiological function of RSA and supports the hypothesis that RSA minimizes the work done by the heart while maintaining physiological levels of arterial CO2. These and other new insights the model provides extend our understanding of the integrative nature of vagal control of the heart.
    Mathematical Biosciences 07/2014; 255. DOI:10.1016/j.mbs.2014.06.015 · 1.49 Impact Factor
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    ABSTRACT: Despite extensive use of the renovascular/Goldblatt model of hypertension–2 K-C, and the use of renal denervation to treat drug resistant hypertensive patients, autonomic mechanisms that underpin the maintenance of this hypertension are important yet remain unclear. Our aim was to analyse cardiovascular autonomic function by power spectral density analysis of both arterial pressure and pulse interval measured continuously by radio telemetry for 6 weeks after renal artery clipping. Mean arterial pressure increased from 106 ± 5 to 185 ± 2 mmHg during 5 weeks post clipping when it stabilized. A tachycardia developed during the 4th week, which plateaued between weeks 5 and 6. The gain of the cardiac vagal baroreflex decreased immediately after clipping and continued to do so until the 5th week when it plateaued (from − 2.4 ± 0.09 to − 0.8 ± 0.04 bpm/mmHg; P < 0.05). A similar time course of changes in the high frequency power spectral density of the pulse interval was observed (decrease from 13.4 ± 0.6 to 8.3 ± 0.01 ms2; P < 0.05). There was an increase in both the very low frequency and low frequency components of systolic blood pressure that occurred 3 and 4 weeks after clipping, respectively. Thus, we show for the first time the temporal profile of autonomic mechanisms underpinning the initiation, development and maintenance of renovascular hypertension including: an immediate depression of cardiac baroreflex gain followed by a delayed cardiac sympathetic predominance; elevated sympathetic vasomotor drive occurring after the initiation of the hypertension but coinciding during its mid-development and maintenance.
    Autonomic neuroscience: basic & clinical 07/2014; 183(100). DOI:10.1016/j.autneu.2014.02.001 · 1.37 Impact Factor

Publication Stats

7k Citations
1,218.90 Total Impact Points


  • 1996–2015
    • University of Bristol
      • School of Physiology and Pharmacology
      Bristol, England, United Kingdom
  • 2014
    • University of Auckland
      • Faculty of Medical and Health Sciences
      Окленд, Auckland, New Zealand
  • 2011
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 2010–2011
    • Drexel University College of Medicine
      • Department of Neurobiology & Anatomy
      Philadelphia, PA, United States
  • 2009
    • University of Florida
      • Department of Physiology and Functional Genomics
      Gainesville, FL, United States
  • 2007
    • Wakayama Medical University
      Wakayama, Wakayama, Japan
    • University of São Paulo
      • Ribeirão Preto School of Medicine (FMRP)
      San Paulo, São Paulo, Brazil
  • 2005
    • Wayne State University
      • Department of Physiology
      Detroit, MI, United States
  • 2003
    • McKnight Brain Institute
      Gainesville, Florida, United States
  • 2002
    • Geisel School of Medicine at Dartmouth
      • Department of Physiology and Neurobiology
      Hanover, New Hampshire, United States
    • University of Tuebingen
      Tübingen, Baden-Württemberg, Germany
  • 2001
    • Drexel University
      • School of Biomedical Engineering, Science and Health Systems
      Philadelphia, PA, United States
    • Case Western Reserve University
      • School of Medicine
      Cleveland, Ohio, United States
  • 1994–1995
    • Georg-August-Universität Göttingen
      • III. Physical Institute
      Göttingen, Lower Saxony, Germany
  • 1991
    • Dupont
      Delaware, Ohio, United States