{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:21:12Z","timestamp":1790169672288,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,12,11]],"date-time":"2008-12-11T00:00:00Z","timestamp":1228953600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:p>Patients with panic disorder provide a clinical model of stress. On a \u201cgood day,\u201d free from a panic attack, they show persistent stress\u2010related changes in sympathetic nerve biology, including abnormal sympathetic nerve single\u2010fiber firing (\u201csalvos\u201d of multiple firing within a cardiac cycle) and release of epinephrine as a cotransmitter. The coreleased epinephrine perhaps originates from <jats:italic>in situ<\/jats:italic> synthesis by phenylethanolamine N\u2010methyltransferase (PNMT). In searching for biological evidence that essential hypertension is caused by mental stress\u2014a disputed proposition\u2014we note parallels with panic disorder, which provides an explicit clinical model of stress: (1) There is clinical comorbidity; panic disorder prevalence is increased threefold in essential hypertension. (2) For both, epinephrine cotransmission is present in sympathetic nerves. (3) In panic disorder and essential hypertension, but not in health, single\u2010fiber sympathetic nerve firing salvos occur. (4) Tissue nerve growth factor is increased in both conditions (nerve growth factor is a stress reactant). (5) There is induction of PNMT in sympathetic nerves. Essential hypertension exhibits a further manifestation of mental stress: there is activation of noradrenergic brain stem neurons projecting to the hypothalamus and amygdala. These pathophysiological findings strongly support the view that chronic mental stress is important in the pathogenesis of essential hypertension. A hypothesis now under test is whether in both disorders, under prevailing conditions of ongoing stress, PNMT induced in sympathetic nerves acts as a DNA methylase, causing the norepinephrine transporter (NET) gene silencing that is present in both conditions. PNMT can have an intranuclear distribution, binding to DNA. We have demonstrated that the reduced neuronal noradrenaline reuptake present in both disorders does have an epigenetic mechanism, with demonstrable reduction in the abundance of the transporter protein, the NET gene silencing being associated with DNA binding by the methylation\u2010related inhibitory transcription factor MeCP2.<\/jats:p>","DOI":"10.1196\/annals.1410.064","type":"journal-article","created":{"date-parts":[[2009,11,6]],"date-time":"2009-11-06T14:56:38Z","timestamp":1257519398000},"page":"338-348","source":"Crossref","is-referenced-by-count":78,"title":["Human Sympathetic Nerve Biology"],"prefix":"10.1196","volume":"1148","author":[{"given":"Murray","family":"Esler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Eikelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Schlaich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlies","family":"Alvarenga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kaye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assam","family":"El\u2010Osta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Barton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciaran","family":"Pier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Brenchley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tye","family":"Dawood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garry","family":"Jennings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,12,11]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"xii","volume-title":"The Nervous System in Arterial Hypertension","author":"Geisbock F.","year":"1976"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.12.4.457"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.300.6730.967"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201X.2003.01089.x"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199311000-00009"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.3109\/08037059409101522"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(99)00237-5"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.100040"},{"key":"e_1_2_6_10_2","first-page":"183","article-title":"Hypertension, SNS overactivity and the brain: Interactions with peripheral organs \u2013 psychological influences and stress and target organ damage","volume":"12","author":"Esler M.","year":"2007","journal-title":"Dialog. 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