ORIGINAL ARTICLE Salt-sensitive men show reduced heart rate variability, lower norepinephrine and enhanced cortisol during mental stress CS Weber 1 , JF Thayer 2,3 , M Rudat 1 , AM Sharma 4 , FH Perschel 5 , K Buchholz 6 and HC Deter 1 1 Department of Psychosomatic Medicine and Psychotherapy, Charite´Universita ¨tsmedizin, Berlin, Germany; 2 Institute of Psychology, Ohio State University, Columbus, OH, USA; 3 Mannheim Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, Heidelberg University, Mannheim, Germany; 4 Department of Medicine, Cardiovascular Obesity Research and Management, McMaster University, Hamilton, Ontario, Canada; 5 Central Institute of Laboratory Medicine and Pathobiochemistry, Charite´ Universita ¨tsmedizin, Berlin, Germany and 6 Department of Internal Medicine IV, Division of Nephrology and General Medicine, University Hospital Freiburg, Freiburg, Germany Salt sensitivity (SS) represents a risk factor for essential hypertension, which has been related to enhanced cardiovascular stress reactivity possibly mediated by increased noradrenergic susceptibility. We investigated biophysiological responses to mental stress in salt-sensitive (ss) and salt-resistant (sr) subjects, hypo- thesizing lower heart rate variability (HRV) and higher cortisol in the ss. A total of 48 healthy normotensive Caucasian men (age 25.6±2.6, body mass index 22.9±2.3) were phenotyped for SS (defined as signifi- cant drop in mean arterial pressure43 mm Hg under the low-salt diet) by a 2-week high- versus low-salt diet. Subjects underwent a standardized mental stress task with continuous cardiovascular monitoring before, dur- ing and after the test (Finapres; Ohmeda, Louisville, CO, USA). Blood samples were drawn to examine cortisol and catecholamines before, after and 20 min after stress. The task elicited significant increases of systolic blood pressure (SBP), diastolic BP (DBP) and heart rate (HR) and a significant decrease of HRV (all time effects Po0.0001). The ss subjects showed lower norepine- phrine (NE) and higher cortisol, indicated by significant group effects (P ¼ 0.009 and 0.025, respectively). HR increased and HRV decreased more in the ss under the stress, shown by significant time by group interactions (P ¼ 0.045 and 0.003, respectively). The observation of a more pronounced HR rise coupled with a greater decrease of HRV in healthy ss men under the influence of brief mental stress confirms their enhanced physio- logical stress reactivity. The lower peripheral NE may represent an effort to compensate for increased nora- drenergic receptor sensitivity. The enhanced cortisol levels are backed by recent genetic findings on HSD11B2 polymorphisms and may promote hypertension. Journal of Human Hypertension (2008) 22, 423–431; doi:10.1038/jhh.2008.11; published online 13 March 2008 Keywords: salt sensitivity; mental stress; heart rate variability; norepinephrine; cortisol Introduction Studies give clear evidence for the clinical relevance of salt sensitivity (SS), especially its association with an increased risk for the development of hypertension. 1 Moreover, SS predicts mortality independently of elevated blood pressure (BP) 2 and proved to be an independent cardiovascular risk factor in Japanese patients with essential hypertension. 3 The underlying pathophysiological mechanisms are still not fully elucidated but renal, 4,5 metabolic, 6 genetic, 7–15 vascular 16,17 and other factors have been implicated. However, literature presents strong evidence for an altered autonomic nervous system (ANS) function. For example, young normotensive salt-sensitive (ss) men showed a significantly higher pressor response to infused norepinephrine (NE) compared to their salt-resistant (sr) counterparts independent of the diet, indicating sympathetic hyperresponsiveness. 18 Increased cardiovascular re- activity to sympathetic stress induced by cold pressure and delayed recovery were observed in ss children. 19 Our group found heightened cardio- vascular reactivity and reduced vagal tone, as indexed by the high frequency (HF) component of heart rate variability (HRV), in young normotensive Received 11 September 2007; revised 19 December 2007; accepted 31 January 2008; published online 13 March 2008 Correspondence: Dr CS Weber, Department of Psychosomatic Medicine and Psychotherapy, Charite ´ Universita ¨tsmedizin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin 12200, Germany. E-mail cora.weber@charite.de Journal of Human Hypertension (2008) 22, 423–431 & 2008 Nature Publishing Group All rights reserved 0950-9240/08 $30.00 www.nature.com/jhh