Point: Chronic Activation of the Sympathetic Nervous System is the Dominant Contributor to Systemic Hypertension
2010; American Physiological Society; Volume: 109; Issue: 6 Linguagem: Inglês
10.1152/japplphysiol.00182.2010
ISSN8750-7587
AutoresMurray Esler, Élisabeth Lambert, Markus P. Schlaich,
Tópico(s)Renin-Angiotensin System Studies
ResumoPOINT:COUNTERPOINTThe dominant contributor to systemic hypertension: chronic activation of the sympathetic nervous system vs. activation of the intrarenal renin-angiotensin systemPoint: Chronic Activation of the Sympathetic Nervous System is the Dominant Contributor to Systemic HypertensionMurray Esler, Elisabeth Lambert, and Markus SchlaichMurray EslerBaker IDI Heart and Diabetes Institute Melbourne, Australia e-mail: , Elisabeth LambertBaker IDI Heart and Diabetes Institute Melbourne, Australia e-mail: , and Markus SchlaichBaker IDI Heart and Diabetes Institute Melbourne, Australia e-mail: Published Online:01 Dec 2010https://doi.org/10.1152/japplphysiol.00182.2010This is the final version - click for previous versionMoreSectionsSupplemental MaterialPDF (100 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat For the past three decades, the renin-angiotensin system has been the major focus in high blood pressure research. The proven value of antihypertensive drugs that block this system has deflected research from other blood pressure-raising systems, including the sympathetic nervous system. Despite this, undeniable evidence exists for the importance of chronic activation of the sympathetic nervous system in the pathogenesis of both experimental and human hypertension.Experimental hypertension.The case appears strongest in the Okamoto-Kyoto hypertensive rat and experimental overfeeding models of obesity-hypertension. Sympathetic nervous system abnormalities catalogued in the spontaneously hypertensive rat importantly include increased efferent sympathetic nerve traffic in younger animals, particularly to the kidneys, with normal nerve firing in older animals (17, 29). Overfeeding in rats, dogs, and rabbits consistently increases body weight, sympathetic nervous activity, and blood pressure, the activation of the renal sympathetic outflow being particularly prominent (11).Human hypertension.Application of sympathetic nerve recording and norepinephrine spillover methodology has demonstrated activation of sympathetic nervous outflows to the kidneys, heart, and skeletal muscle vasculature, typically a doubling or trebling overall, in patients with essential hypertension (7, 8, 13, 14, 16, 20, 24). The syndrome of neurogenic essential hypertension appears to account for no less than 50% of all cases of high blood pressure. This estimate is based on both the proportion of patients with essential hypertension who have demonstrable sympathetic excitation and the number in whom substantial blood pressure lowering is achieved with antiadrenergic drugs or devices (19, 22). Multiple studies from different research groups (1, 7–10, 13, 14, 16, 20, 24, 25, 30), identify activated sympathetic outflow to the skeletal muscle vasculature, heart, and kidneys in 40–65% of patients (notably, the cardiac sympathetic outflow is spared in obesity-hypertension), with the caveat that in those aged more than 60 yr, although MSNA is increased, cardiac and renal norepinephrine spillover is typically normal. Single fiber sympathetic recording demonstrates increased firing frequencies (16, 20) and multiple firings within a cardiac cycle (firing salvos), not seen in health (20). Sympathetic nervous activation also characterizes human renal hypertension. In end-stage renal disease, sympathetic nervous activation is at a high level, equal to or exceeding that seen in cardiac failure (4,15).Does this sympathetic activation cause the blood pressure elevation ?Once it was thought that the sympathetic nervous system exerts minute by minute circulatory control only and was not of importance in the pathogenesis of hypertension. The regulatory effects of the renal sympathetic nerves on renin release, glomerular filtration rate, and renal tubular reabsorption of sodium are, however, now seen to provide a range of potential hypertension-producing mechanisms. Experimental studies establish the important concept that subvasoconstrictor levels of renal sympathetic activity can increase renin secretion and renal sodium retention, without changing renal hemodynamics (5). Of relevance, younger patients with mild essential hypertension very commonly have "high renin essential hypertension," where renal sympathetic activity is sufficiently elevated to increase renal secretion of renin, but not to reduce renal blood flow (8, 9, 24). Renin-angiotensin inhibitors work well in these patients, in part because they are countering neurally mediated RAS activation.Human hypertension.Does this sympathetic activation initiate and maintain the blood pressure elevation in patients with essential hypertension? There is strong evidence to support this claim, both historical and contemporary. In earlier times, prior to the availability of antihypertensive drugs, extensive surgical sympathectomy was effectively used as a treatment of severe hypertension (28). Of the antihypertensive drugs subsequently developed from the mid-20th century, many were antiadrenergic. The recent case made against β-adrenergic blocker prescribing in hypertension is based on the adverse metabolic side effects of this drug class, and certainly not a lack of blood pressure lowering efficacy.In end-stage renal disease, renal transplantation restores renal function but does not abolish the hypertension. Nephrectomy does through normalizing sympathetic tone (4, 15) via removal of the sympathetic excitatory influence of renal afferents from the failed kidneys (3). The hypertension of renal failure is explicitly a neurogenic hypertension (4, 15, 27).Experimental renal denervation.In multiple forms (5) of experimental hypertension renal denervation completely prevents, delays the onset of, or ameliorates the magnitude of the hypertension. Where examined, the beneficial effect of renal denervation on the hypertension was associated with a concurrent decrease in renal sodium retention (5).The "bottom line": the antihypertensive effect of renal sympathetic denervation in resistant essential hypertension.The sympathetic nervous system is the "forgotten pathway" in hypertension treatment. This may soon change, with the recent testing of device-based therapies, including the surgically implantable arterial barostimulator, in patients with hypertension (22). Another revolutionary treatment principle recently successfully tested in patients with drug-resistant essential hypertension (19, 26) involves bilateral ablation of the renal sympathetic nerves with a purpose-developed radiofrequency emitting catheter (the Symplicity catheter, Ardian Corporation, Palo Alto, CA). The catheter is inserted percutaneously via the femoral artery to lie in the renal artery lumen, and radiofrequency energy is delivered in 90° quadrants in stepwise fashion to the full circumference of both renal arteries (19). Sympathetic nerves enter the human kidneys in the renal artery walls, within reach of ablative energy delivery.The study established that the procedure does produce renal denervation, that it is safe, and that blood pressure is lowered (19, 26). Blood pressure fell markedly, with a mean fall of 24/10 mmHg at 3 mo and 27/13 mmHg at 12 mo (P < 0.001;l Ref. 19). At this point (with the longest follow-up in participants being 2 yr), blood pressure reduction is sustained, suggesting that if renal sympathetic reinnervation occurs it is insufficient to cancel out the blood pressure benefit (Fig. 1).Fig. 1.Fall in blood pressure after an endovascular bilateral renal sympathetic denervation procedure in patients with hypertension resistant to treatment with multiple antihypertensive drugs, including a diuretic. Notably, all patients were under treatment with an ACE inhibitor or angiotensin receptor blocker (or both). The patients shown represent the initial treatment cohort (19), with subsequent ongoing surveillance of these patients and additional recruitment. Histogram depicts the changes in clinic systolic and diastolic pressures at differing follow up time points (M = months postprocedure). Number of patients at each time point is indicated in brackets.Download figureDownload PowerPointThe renin-angiotensin system in hypertension: science and metaphysics?Given that antihypertensive drugs antagonizing the renin-angiotensin system are the dominant therapy, how can a case for pre-eminence of sympathetic neural origins of human hypertension be sustained? Drug prescribing practices in hypertension, however, manifestly do not prove pathogenesis. In any era, the drug class used most widely for an illness commonly dictates which research stream is followed for the illness (especially if the drug patents have not expired!), determining the prevailing notions of pathophysiology. But there is a logical flaw in attempting to ascertain the biology of a disease from the presumed mode of action of an efficacious drug, very evident with psychotropic drugs (12), and applying also in essential hypertension.Despite the current dominance in therapy of drugs antagonizing the renin-angiotensin system, plasma renin levels in essential hypertension are often low (2), when plasma renin activity is high this typically has a neural mechanism, high sympathetic outflow to the kidneys stimulating renin release (8, 9), the clinical case made for specific therapeutic benefit with renin-angiotensin inhibitors has been claimed by eminent educators to have, in fact, been overstated (18, 21), and the importance of a cellular, extrarenal renin-angiotensin system, often invoked since plasma renin values are unremarkable in hypertension, is disputed (23). Well known to clinicians and experimenters alike is the diagram, now iconic (6) and generously used in pharmaceutical marketing, of the "Renin-Angiotensin Based Cardiovascular Continuum," where the path from cardiac risk factors, through to myocardial infarction, cardiac arrhythmias, heart failure, and death has angiotensin as the noxious prime mover at every step (6). This construction, although true in parts, is as much metaphysics as science, and leaves little place for the sympathetic nervous system to claim its birthright!REFERENCES1. Anderson EA , Sinkey CA , Lawton WJ , Mark AL. Elevated sympathetic nerve activity in borderline hypertensive humans: evidence from direct intraneural recordings. Hypertension 14: 177–183, 1989.Crossref | PubMed | ISI | Google Scholar2. Buhler FR , Laragh JH , Baer L , Vaughan ED , Brunner HR. Propranolol inhibition of renin secretion. New Engl J Med 287: 1209–1214, 1972.Crossref | PubMed | ISI | Google Scholar3. Campese VM , Kogosov E. Renal afferent denervation prevents hypertension in rats with chronic renal failure. Hypertension 25: 878–882, 1995.Crossref | PubMed | ISI | Google Scholar4. Converse RL , Jacobsen TN , Toto RD , Jost CMT , Cosentino F , Fouad-Tarazi F , Victor RG. Sympathetic overactivity in patients with chronic renal failure. N Engl J Med 327: 1912–1918, 1992.Crossref | PubMed | ISI | Google Scholar5. DiBona GF , Kopp UC. Neural control of renal function. Physiol Rev 77: 76–197, 1997.Link | ISI | Google Scholar6. Dzau V , Braunwald E. Resolved and unresolved issues in the prevention and treatment of coronary artery disease; A workshop consensus statement. Am Heart J 121: 1244–1263, 1991.Crossref | ISI | Google Scholar7. Esler M , Jennings G , Korner P , Willett I , Dudley F , Hasking G , Anderson W , Lambert G. The assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover. Hypertension 11: 3–20, 1988.Crossref | PubMed | ISI | Google Scholar8. Esler M , Lambert G , Jennings G. Regional norepinephrine turnover in human hypertension. Clin Exp Hypertens 11, Suppl 1: 75–89, 1989.ISI | Google Scholar9. Esler M. Sympathetic activity in experimental and human hypertension. In: Handbook of Hypertension, Volume 17: Pathophysiology of Hypertension, edited by , Mancia G , Zanchetti A. Amsterdam: Elsevier, 1997, p. 628–673.Google Scholar10. Esler M. Looking at the sympathetic nervous system as a primary source. In: Handbook of Hypertension: Hypertension Research in the Twentieth Century, edited by , Zanchetti A , Robertson JIS , Birkenhager WH. Elsevier: Amsterdam, 2004, p. 81–103.Google Scholar11. Esler M , Straznicky N , Eikelis N , Masuo K , Lambert G , Lambert E. Mechanisms of sympathetic activation in obesity-related hypertension. Hypertension 48: 787–796, 2006.Crossref | PubMed | ISI | Google Scholar12. Esler M , Lambert E , Alvarenga M , Socratous F , Richards J , Barton D , Pier C , Brenchley C , Dawood T , Hastings J , Guo L , Haikerwal D , Kaye D , Jennings G , Kalff V , Kelly M , Wiesner G , Lambert G. Increased brain serotonin turnover in panic disorder patients in the absence of a panic attack: reduction by a selective serotonin reuptake inhibitor. Stress 10: 295–304, 2007.Crossref | ISI | Google Scholar13. Grassi G , Colombo M , Seravalle G , Spaziani D , Mancia G. Dissociation between muscle and skin sympathetic nerve activity in essential hypertension, obesity, and congestive heart failure. Hypertension 31: 64–67, 1998.Crossref | PubMed | ISI | Google Scholar14. Grassi G , Dell'Oro R , Quarti-Trevano F , Scopelliti F , Seravalle G , Paleari F , Gamba PL , Mancia G. Neuroadrenergic and reflex abnormalities in patients with the metabolic syndrome. Diabetologia 48: 1359–1365, 2005.Crossref | PubMed | ISI | Google Scholar15. Hausberg M , Kosch M , Harmelink P , Barenbrock M , Hohage H , Kisters K , Dietl KH , Rahn KH. Sympathetic nerve activity in end-stage renal disease. Circulation 106: 1974–1979, 2002.Crossref | PubMed | ISI | Google Scholar16. Huggett RJ , Burns J , MackIntosh AF , Mary DASG. Sympathetic neural activation in nondiabetic metabolic syndrome and its further augmentation by hypertension. Hypertension 44: 1–6, 2004.Crossref | PubMed | ISI | Google Scholar17. Judy WV , Watanabe AM , Murphy WR , Aprison BS , Yu PI. Sympathetic nerve activity and blood pressure in normotensive back-cross rats genetically related to the spontaneously hypertensive rat. Hypertension 1: 598–604, 1979.Crossref | PubMed | ISI | Google Scholar18. Kaplan NM. Clinical trials for hypertension. Expectations fulfilled and unfulfilled. Hypertension 49: 257–259, 2007.Crossref | ISI | Google Scholar19. Krum H , Schlaich MP , Whitbourn R , Sobotka P , Sadowski J , Bartus K , Kapelak B , Walton A , Sievert H , Thambar S , Abraham WT , Esler M. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet 373: 1275–1281, 2009.Crossref | PubMed | ISI | Google Scholar20. Lambert E , Straznicky N , Schlaich MP , Dawood T , Hotchkin E , Esler MD , Lambert GW. Differing patterns of sympathoexcitation in normal weight and obesity-related hypertension. Hypertension 50: 862–868, 2007.Crossref | PubMed | ISI | Google Scholar21. Messerli FH , Staessen JA. Amlodipine better than lisinopril? How one randomized clinical trial ended fallacies from observational studies. Hypertension 48: 359–361, 2006.Crossref | ISI | Google Scholar22. Mohaupt MG , Schmidli J , Luft FC. Management of uncontrollable hypertension with a carotid sinus stimulation device. Hypertension 50: 825–828, 2007.Crossref | PubMed | ISI | Google Scholar23. Reudelhuber TL. Truncated prorenin comes up… short. Hypertension 54: 1216–1217, 2009.Crossref | ISI | Google Scholar24. Rumantir MS , Vaz M , Jennings GL , Collier G , Kaye DM , Seals DR , Wiesner GH , Brunner-La Rocca HP , Esler MD. Neural mechanisms in human obesity-related hypertension. J Hypertens 17: 1125–1133, 1999.Crossref | PubMed | ISI | Google Scholar25. Schlaich MP , Lambert E , Kaye DM , Krozowski Z , Campbell DJ , Lambert G , Hastings J , Aggarwal A , Esler MD. Sympathetic nervous augmentation in essential hypertension: role of nerve firing, norepinephrine reuptake and angiotensin neuromodulation. Hypertension 43: 169–175, 2004.Crossref | PubMed | ISI | Google Scholar26. Schlaich MP , Sobotka PA , Krum H , Lambert E , Esler MD. Renal sympathetic nerve ablation for the treatment of uncontrolled hypertension. N Engl J Med 361: 932–934, 2009.Crossref | PubMed | ISI | Google Scholar27. Schlaich MP , Socratous F , Hennebry S , Eikelis N , Lambert EA , Straznicky N , Esler MD , Lambert GW. Sympathetic activation in chronic renal failure. J Am Soc Nephrol 20: 933–939, 2009.Crossref | PubMed | ISI | Google Scholar28. Smithwick RH , Bush RD , Kinsey D , Whitelaw GP. Hypertension and associated cardiovascular disease; comparison of male and female mortality rates and their influence on selection of therapy. J Am Med Assoc 160: 1023–1026, 1956.Crossref | PubMed | ISI | Google Scholar29. Thorén P. Efferent renal nerve traffic in SHR. Clin Exp Hypertens 9, Suppl 1: 259–279, , 1987.ISI | Google Scholar30. Yamada Y , Miyajima E , Tochikubo O , Matsukawa AT , Ishii M. Age-related changes in muscle sympathetic nerve activity in essential hypertension. Hypertension 13: 870–877, 1989.Crossref | PubMed | ISI | Google ScholarSupplemental datadescriptions.docx (12.82 kb) Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation Cited ByNovel approaches: targeting sympathetic outflow in the carotid sinus20 July 2023 | Blood Pressure, Vol. 32, No. 1Development and validation of a nomogram model for individualized prediction of hypertension risk in patients with type 2 diabetes mellitus23 January 2023 | Scientific Reports, Vol. 13, No. 1Causes and consequences of sympathoexcitation across the lifespan: Physiological or pathological?15 September 2023 | Experimental Physiology, Vol. 244Comparative analysis of intracardiac neural structures in the aged rats with essential hypertension7 November 2022 | The Anatomical Record, Vol. 306, No. 9Central Autonomic Network Regions and Hypertension: Unveiling Sympathetic Activation and Genetic Therapeutic Perspectives21 August 2023 | Biology, Vol. 12, No. 8Anti-hypertensive medication adherence in the REQUIRE trial: post-hoc exploratory evaluation1 June 2023 | Hypertension Research, Vol. 46, No. 8Review Article on Molecular Mechanism of Regulation of Hypertension by Macro-elements (Na, K, Ca and Mg), Micro-elements/Trace Metals (Zn and Cu) and Toxic Elements (Pb and As)31 July 2023 | Biological Trace Element Research, Vol. 31Central and peripheral chemoreflexes in humans with treated hypertension14 April 2023 | The Journal of Physiology, Vol. 601, No. 12Renal sympathetic activity: A key modulator of pressure natriuresis in hypertensionBiochemical Pharmacology, Vol. 208Sensitization of Hypertension: The Impact of Earlier Life Challenges: Excellence Award for Hypertension Research 2021Hypertension, Vol. 80, No. 1Diverse pharmacological properties, trial results, comorbidity prescribing and neural pathophysiology suggest European hypertension guideline downgrading of beta-blockers is not justified26 August 2022 | Blood Pressure, Vol. 31, No. 1Clinical Status of Cardiac Rehabilitation Manners and ModelsCardiology Research and Practice, Vol. 2022A Japan nationwide web-based survey of patient preference for renal denervation for hypertension treatment17 October 2021 | Hypertension Research, Vol. 45, No. 2The sympathies of the body: functional organization and neuronal differentiation in the peripheral sympathetic nervous system10 November 2021 | Cell and Tissue Research, Vol. 386, No. 3Differential influences of dietary sodium on blood pressure regulation based on race and sexAutonomic Neuroscience, Vol. 236Centrally acting antihypertensives change the psychogenic cardiovascular reactivity27 February 2021 | Fundamental & Clinical Pharmacology, Vol. 35, No. 5Renal interventions in the management of hypertension29 April 2021 | Current Opinion in Cardiology, Vol. 36, No. 4Further evidence against the role renal medullary perfusion in short-term control of arterial pressure in normotensive and mildly or overtly hypertensive rats2 March 2021 | Pflügers Archiv - European Journal of Physiology, Vol. 473, No. 4Effect of Moderate- Versus High-Intensity Interval Exercise Training on Heart Rate Variability Parameters in Inactive Latin-American Adults: A Randomized Clinical TrialJournal of Strength and Conditioning Research, Vol. 34, No. 12Altered renal medullary blood flow: A key factor or a parallel event in control of sodium excretion and blood pressure?7 April 2020 | Clinical and Experimental Pharmacology and Physiology, Vol. 47, No. 8Evaluation of elevated heart rate as a sympathetic nervous system biomarker in essential hypertension13 March 2020 | Journal of Hypertension, Vol. 38, No. 8Stress, Hypertension and Yoga13 May 2020Gut microbiota and neuroinflammation in pathogenesis of hypertension: A potential role for hydrogen sulfidePharmacological Research, Vol. 153Neuroimmune crosstalk in the pathophysiology of hypertension20 March 2019 | Nature Reviews Cardiology, Vol. 16, No. 8Maternal Protein Restriction in Two Successive Generations Impairs Mitochondrial Electron Coupling in the Progeny's Brainstem of Wistar Rats From Both Sexes14 March 2019 | Frontiers in Neuroscience, Vol. 13Does increased 24-h ambulatory heart rate identify de facto neurogenic hypertension, and facilitate selection of hypertensive patients for renal denervation?7 February 2019 | European Heart Journal, Vol. 40, No. 9Plant-Based Ethnopharmacological Remedies for Hypertension in Suriname30 January 2019A Three-Arm Randomized Trial of Different Renal Denervation Devices and Techniques in Patients With Resistant Hypertension (RADIOSOUND-HTN)Circulation, Vol. 139, No. 5Status of Renal Denervation Therapy for HypertensionCirculation, Vol. 139, No. 5Morphological and Functional Characteristics of Blood and Lymphatic Vessels9 May 2019The Protective Role of Estrogen and Brain Estrogen Receptors in the Pathogenesis of HypertensionFrontiers in Physiology, Vol. 10Evidence against a crucial role of renal medullary perfusion in blood pressure control of hypertensive rats10 November 2018 | The Journal of Physiology, Vol. 597, No. 1Central nervous system neuroplasticity and the sensitization of hypertension18 October 2018 | Nature Reviews Nephrology, Vol. 14, No. 12Fine tuning renal denervationJournal of Hypertension, Vol. 36, No. 12Control of renal sympathetic nerve activity by neurotransmitters in the spinal cord in Goldblatt hypertensionBrain Research, Vol. 1698Neuroinflammation and sympathetic overactivity: Mechanisms and implications in hypertensionAutonomic Neuroscience, Vol. 210A Calibrated Method of Massage Therapy Decreases Systolic Blood Pressure Concomitant With Changes in Heart Rate Variability in Male RatsJournal of Manipulative and Physiological Therapeutics, Vol. 40, No. 2Renal Denervation Reduces Monocyte Activation and Monocyte–Platelet Aggregate FormationHypertension, Vol. 69, No. 2Exercise training-induced modification in autonomic nervous system: An update for cardiac patientsAnnals of Physical and Rehabilitation Medicine, Vol. 60, No. 1Normotension, hypertension and body fluid regulation: brain and kidney19 June 2016 | Acta Physiologica, Vol. 219, No. 1Sympathetic neurons are a powerful driver of myocyte function in cardiovascular disease14 December 2016 | Scientific Reports, Vol. 6, No. 1Different blood pressure responses to opioids in 3 rat hypertension models: role of the baseline status of sympathetic and renin–angiotensin systemsCanadian Journal of Physiology and Pharmacology, Vol. 94, No. 11Renal denervation in the treatment of resistant hypertension: Dead, alive or surviving?Revista Portuguesa de Cardiologia, Vol. 35, No. 10Renal denervation in the treatment of resistant hypertension: Dead, alive or surviving?Revista Portuguesa de Cardiologia (English Edition), Vol. 35, No. 10Peroxisome proliferator-activated receptor-α stimulation by clofibrate favors an antioxidant and vasodilator environment in a stressed left ventriclePharmacological Reports, Vol. 68, No. 4Hypertension: a problem of organ blood flow supply–demand mismatchFuture Cardiology, Vol. 12, No. 3Reply1 March 2016 | Experimental Physiology, Vol. 101, No. 3Sympathetic regulation of blood pressure in normotension and hypertension: when sex matters1 February 2016 | Experimental Physiology, Vol. 101, No. 2Pathophysiology of Hypertension in Chronic Kidney Disease and Dialysis13 October 2016Pathophysiology of Renal Sympathetic Denervation (RSDN)3 August 2016Psychogenic Hypertension1 June 2016Blood Pressure: Return of the Sympathetics?7 January 2016 | Current Hypertension Reports, Vol. 18, No. 1Sympathetic overactivity occurs before hypertension in the two-kidney, one-clip model14 December 2015 | Experimental Physiology, Vol. 101, No. 1The roles of sensitization and neuroplasticity in the long-term regulation of blood pressure and hypertensionAlan Kim Johnson, Zhongming Zhang, Sarah C. Clayton, Terry G. Beltz, Seth W. Hurley, Robert L. Thunhorst, and Baojian Xue1 December 2015 | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 309, No. 11Misconceptions and Facts About Treating HypertensionThe American Journal of Medicine, Vol. 128, No. 5The role of renal nerves in cardiovascular and renal function in normal and pathophysiological states6 May 2015 | Experimental Physiology, Vol. 100, No. 5Mechanisms of renal sympathetic activation in renovascular hypertension6 May 2015 | Experimental Physiology, Vol. 100, No. 5The crosstalk between the kidney and the central nervous system: the role of renal nerves in blood pressure regulation20 January 2015 | Experimental Physiology, Vol. 100, No. 5Na + /Ca 2+ exchange and Na + /K + -ATPase in the heart13 March 2015 | The Journal of Physiology, Vol. 593, No. 6The Sympathetic Nervous System Alterations in Human HypertensionCirculation Research, Vol. 116, No. 6Is the failure of SYMPLICITY HTN-3 trial to meet its efficacy endpoint the "end of the road" for renal denervation?Journal of the American Society of Hypertension, Vol. 9, No. 2Renal denervation for resistant hypertensionRevista Portuguesa de Cardiologia, Vol. 34, No. 2Renal denervation for resistant hypertensionRevista Portuguesa de Cardiologia (English Edition), Vol. 34, No. 2Psychogenic Hypertension29 December 2015Methods of sympathetic activity evaluation in patients with systemic refractory hypertension15 December 2014 | Systemic Hypertension, Vol. 11, No. 4Gastrointestinal Intervention Ameliorates High Blood Pressure Through Antagonizing Overdrive of the Sympathetic Nerve in Hypertensive Patients and RatsJournal of the American Heart Association, Vol. 3, No. 5Physiology: hemodynamics, endothelial function, renin–angiotensin–aldosterone system, sympathetic nervous systemJournal of the American Society of Hypertension, Vol. 8, No. 7Renal denervation for hypertension: observations and predictions of a founder4 March 2014 | European Heart Journal, Vol. 35, No. 18Sympathetic Nervous System Moves Toward Center Stage in Cardiovascular MedicineHypertension, Vol. 63, No. 3Brain Stem NOS and ROS in Neural Mechanisms of HypertensionAntioxidants & Redox Signaling, Vol. 20, No. 1Discharge of RVLM vasomotor neurons is not increased in anesthetized angiotensin II-salt hypertensive ratsGustavo R. 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