{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T05:21:43Z","timestamp":1778908903299,"version":"3.51.4"},"reference-count":37,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,7,1]]},"abstract":"<jats:p>Patients with neurogenic orthostatic hypotension (OH) typically have impaired sympathetic nervous system tone and therefore low levels of upright plasma norepinephrine (NE) (noradrenaline). We report a subset of patients who clinically have typical neurogenic OH but who paradoxically have elevated upright levels of plasma NE. We retrospectively studied 83 OH patients evaluated at the Vanderbilt Autonomic Dysfunction Center between August 2007 and May 2013. Based on standing NE, patients were dichotomized into a hyperadrenergic OH group [hyperOH: upright NE \u2265 3.55 nmol\/l (600 pg\/ml), n=19] or a non-hyperadrenergic OH group [nOH: upright NE &amp;lt; 3.55 nmol\/l (600 pg\/ml), n=64]. Medical history and data from autonomic testing, including the Valsalva manoeuvre (VM), were analysed. HyperOH patients had profound orthostatic falls in blood pressure (BP), but less severe than in nOH [change in SBP (systolic blood pressure): \u221253\u00b131 mmHg compared with \u221268\u00b133 mmHg, P=0.050; change in DBP (diastolic blood pressure): \u221218\u00b123 mmHg compared with \u221230\u00b117 mmHg, P=0.01]. The expected compensatory increase in standing heart rate (HR) was similarly blunted in both hyperOH and nOH groups [84\u00b115 beats per minute (bpm) compared with 82\u00b114 bpm; P=0.6]. HyperOH patients had less severe sympathetic failure as evidenced by smaller falls in DBP during phase 2 of VM and a shorter VM phase 4 BP recovery time (16.5\u00b18.9\u00a0s compared with 31.6\u00b116.6\u00a0s; P&amp;lt;0.001) than nOH patients. Neurogenic hyperOH patients have severe neurogenic OH, but have less severe adrenergic dysfunction than nOH patients. Further work is required to understand whether hyperOH patients will progress to nOH or whether this represents a different disorder.<\/jats:p>","DOI":"10.1042\/cs20140766","type":"journal-article","created":{"date-parts":[[2015,2,23]],"date-time":"2015-02-23T16:23:00Z","timestamp":1424708580000},"page":"107-116","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Neurogenic hyperadrenergic orthostatic hypotension: a newly recognized variant of orthostatic hypotension in older adults with elevated norepinephrine (noradrenaline)"],"prefix":"10.1042","volume":"129","author":[{"given":"Philip\u00a0L.","family":"Mar","sequence":"first","affiliation":[{"name":"Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A."},{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of Louisville, Louisville, KY 40270-9941, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cyndya\u00a0A.","family":"Shibao","sequence":"additional","affiliation":[{"name":"Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily\u00a0M.","family":"Garland","sequence":"additional","affiliation":[{"name":"Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bonnie\u00a0K.","family":"Black","sequence":"additional","affiliation":[{"name":"Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Italo","family":"Biaggioni","sequence":"additional","affiliation":[{"name":"Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A."},{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-2102, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Diedrich","sequence":"additional","affiliation":[{"name":"Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A."},{"name":"Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232-2102, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachin\u00a0Y.","family":"Paranjape","sequence":"additional","affiliation":[{"name":"Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Robertson","sequence":"additional","affiliation":[{"name":"Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A."},{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-2102, U.S.A."},{"name":"Department of Neurology, Vanderbilt University, Nashville, TN 37212-2102, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satish\u00a0R.","family":"Raj","sequence":"additional","affiliation":[{"name":"Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A."},{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-2102, U.S.A."},{"name":"Department of Cardiac Science, Libin Cardiovascular Institute, University of Calgary, Calgary, AB T2N 2T9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2015,4,24]]},"reference":[{"key":"2021113010402588600_B1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s10286-011-0119-5","article-title":"Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome","volume":"21","author":"Freeman","year":"2011","journal-title":"Clin. Auton. Res."},{"key":"2021113010402588600_B2","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1007\/s10286-007-1001-3","article-title":"Prevalence of orthostatic hypotension","volume":"18","author":"Low","year":"2008","journal-title":"Clin. Auton. Res."},{"key":"2021113010402588600_B3","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1111\/j.1365-2710.2005.00629.x","article-title":"High prevalence of orthostatic hypotension and its correlation with potentially causative medications among elderly veterans","volume":"30","author":"Poon","year":"2005","journal-title":"J. Clin. Pharm. Ther."},{"key":"2021113010402588600_B4","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1016\/j.amjmed.2007.05.009","article-title":"Orthostatic hypotension-related hospitalizations in the United States","volume":"120","author":"Shibao","year":"2007","journal-title":"Am. J. Med."},{"key":"2021113010402588600_B5","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1001\/archinte.1994.00420140086011","article-title":"Causes of chronic orthostatic hypotension","volume":"154","author":"Robertson","year":"1994","journal-title":"Arch. Intern. Med."},{"key":"2021113010402588600_B6","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1056\/NEJM197702102960601","article-title":"The sympathetic-nervous-system defect in primary orthostatic hypotension","volume":"296","author":"Ziegler","year":"1977","journal-title":"N. Engl. J. Med."},{"key":"2021113010402588600_B7","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1172\/JCI114878","article-title":"Pathogenesis of hyperadrenergic orthostatic hypotension. Evidence of disordered venous innervation exclusively in the lower limbs","volume":"86","author":"Streeten","year":"1990","journal-title":"J. Clin. Invest"},{"key":"2021113010402588600_B8","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1152\/jappl.1998.84.3.914","article-title":"Effect of standing on neurohumoral responses and plasma volume in healthy subjects","volume":"84","author":"Jacob","year":"1998","journal-title":"J. Appl. Physiol."},{"key":"2021113010402588600_B9","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.parkreldis.2011.04.016","article-title":"Prevalence of orthostatic hypotension in Parkinson's disease: a systematic review and meta-analysis","volume":"17","author":"Velseboer","year":"2011","journal-title":"Parkinsonism Relat. Disord."},{"key":"2021113010402588600_B10","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1161\/01.CIR.96.2.575","article-title":"Effects of volume loading and pressor agents in idiopathic orthostatic tachycardia","volume":"96","author":"Jacob","year":"1997","journal-title":"Circulation"},{"key":"2021113010402588600_B11","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1109\/TBME.1985.325532","article-title":"A real-time QRS detection algorithm","volume-title":"IEEE Trans. Biomed. Eng.","author":"Pan","year":"1985"},{"key":"2021113010402588600_B12","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1161\/01.CIR.93.5.1043","article-title":"Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology","volume":"93","author":"Malik","year":"1996","journal-title":"Circulation"},{"key":"2021113010402588600_B13","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1097\/00004872-200309000-00017","article-title":"The sympathetic nervous system in hypertension: assessment by blood pressure variability and ganglionic blockade","volume":"21","author":"Diedrich","year":"2003","journal-title":"J. Hypertens."},{"key":"2021113010402588600_B14","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1161\/01.CIR.93.5.1043","article-title":"Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology","volume":"93","year":"1996","journal-title":"Circulation"},{"key":"2021113010402588600_B15","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1097\/00004872-200110000-00001","article-title":"Time versus frequency domain techniques for assessing baroreflex sensitivity","volume":"19","author":"Persson","year":"2001","journal-title":"J. Hypertens."},{"key":"2021113010402588600_B16","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1152\/jappl.1991.71.4.1563","article-title":"Pharmacological dissection of components of the Valsalva maneuver in adrenergic failure","volume":"71","author":"Sandroni","year":"1991","journal-title":"J. Appl. Physiol."},{"key":"2021113010402588600_B17","doi-asserted-by":"publisher","first-page":"2010","DOI":"10.1212\/WNL.0b013e31821e5563","article-title":"Assessment of sympathetic index from the Valsalva maneuver","volume":"76","author":"Novak","year":"2011","journal-title":"Neurology"},{"key":"2021113010402588600_B18","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1212\/01.wnl.0000184504.13173.ef","article-title":"Blood pressure recovery from Valsalva maneuver in patients with autonomic failure","volume":"65","author":"Vogel","year":"2005","journal-title":"Neurology"},{"key":"2021113010402588600_B19","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1001\/archneur.64.3.381","article-title":"Adrenergic and vagal baroreflex sensitivity in autonomic failure","volume":"64","author":"Schrezenmaier","year":"2007","journal-title":"Arch. Neurol."},{"key":"2021113010402588600_B20","doi-asserted-by":"publisher","first-page":"e000700","DOI":"10.1161\/JAHA.113.000700","article-title":"Postural tachycardia syndrome and inappropriate sinus tachycardia: role of autonomic modulation and sinus node automaticity","volume":"3","author":"Nwazue","year":"2014","journal-title":"J. Am. Heart Assoc."},{"key":"2021113010402588600_B21","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1056\/NEJMcp074189","article-title":"Clinical practice. Neurogenic orthostatic hypotension","volume":"358","author":"Freeman","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"2021113010402588600_B22","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1556\/APhysiol.99.2012.2.4","article-title":"Haemodynamic parameters and cognitive function during modeled acute volume loss","volume":"99","author":"Tuboly","year":"2012","journal-title":"Acta Physiol. Hung."},{"key":"2021113010402588600_B23","first-page":"H1691","article-title":"Human sympathetic and vagal baroreflex responses to sequential nitroprusside and phenylephrine","volume":"276","author":"Rudas","year":"1999","journal-title":"Am. J. Physiol."},{"key":"2021113010402588600_B24","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1002\/mds.21839","article-title":"Survival in multiple system atrophy","volume":"23","author":"Schrag","year":"2008","journal-title":"Mov. Disord."},{"key":"2021113010402588600_B25","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1016\/S1474-4422(09)70288-1","article-title":"Multiple system atrophy: an update","volume":"8","author":"Stefanova","year":"2009","journal-title":"Lancet Neurol."},{"key":"2021113010402588600_B26","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1136\/jnnp.2004.049023","article-title":"Progression and prognosis in pure autonomic failure (PAF): comparison with multiple system atrophy","volume":"76","author":"Mabuchi","year":"2005","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"2021113010402588600_B27","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/j.1532-5415.1999.tb01898.x","article-title":"Drugs and falls in older people: a systematic review and meta-analysis: I. Psychotropic drugs","volume":"47","author":"Leipzig","year":"1999","journal-title":"J. Am. Geriatr. Soc."},{"key":"2021113010402588600_B28","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/0002-9149(85)90582-X","article-title":"Effect of a benzodiazepine (alprazolam) on plasma epinephrine and norepinephrine levels during exercise stress","volume":"56","author":"Stratton","year":"1985","journal-title":"Am. J. Cardiol."},{"key":"2021113010402588600_B29","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/clpt.1980.146","article-title":"Sedative and cardiovascular effects of clonidine and nitrazepam","volume":"28","author":"Hossmann","year":"1980","journal-title":"Clin. Pharmacol. Ther."},{"key":"2021113010402588600_B30","first-page":"R400","article-title":"Blood pressure and norepinephrine spillover during propranolol infusion in humans","volume":"248","author":"Best","year":"1985","journal-title":"Am. J. Physiol."},{"key":"2021113010402588600_B31","first-page":"E999","article-title":"Beta-adrenergic blockade decreases norepinephrine release in humans","volume":"258","author":"Rosen","year":"1990","journal-title":"Am. J. Physiol."},{"key":"2021113010402588600_B32","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1007\/s11910-014-0473-5","article-title":"Diabetic neuropathy: mechanisms, emerging treatments, and subtypes","volume":"14","author":"Albers","year":"2014","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"2021113010402588600_B33","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1042\/cs0600217","article-title":"Age-dependence of noradrenaline kinetics in normal subjects","volume":"60","author":"Esler","year":"1981","journal-title":"Clin. Sci."},{"key":"2021113010402588600_B34","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.arcmed.2005.01.003","article-title":"Pathogenesis of type\u00a02 diabetes mellitus","volume-title":"Arch. Med. Res.","author":"Leahy","year":"2005"},{"key":"2021113010402588600_B35","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1172\/JCI7231","article-title":"The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type\u00a02 diabetes mellitus","volume":"104","author":"Weyer","year":"1999","journal-title":"J. Clin. Invest."},{"key":"2021113010402588600_B36","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1016\/j.metabol.2004.02.012","article-title":"Insulin secretion and insulin sensitivity at different stages of glucose tolerance: a cross-sectional study of Japanese type\u00a02 diabetes","volume":"53","author":"Fukushima","year":"2004","journal-title":"Metabolism"},{"key":"2021113010402588600_B37","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1023\/A:1008331930548","article-title":"Monitoring hypovolemia in healthy elderly subjects by measuring blood pressure response to Valsalva's maneuver","volume":"9","author":"van Kraaij","year":"1999","journal-title":"Geriatr. Nephrol. Urol."}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/129\/2\/107\/443955\/cs1290107.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/129\/2\/107\/443955\/cs1290107.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T11:30:35Z","timestamp":1638271835000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/129\/2\/107\/71316\/Neurogenic-hyperadrenergic-orthostatic-hypotension"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,24]]},"references-count":37,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,7,1]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20140766","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,24]]}}}