Anxiety-induced plasma norepinephrine augmentation increases reactive oxygen species formation by monocytes in essential hypertension.
BACKGROUND
An association between anxiety and depression and increased blood pressure (BP) and cardiovascular disease risk has not been firmly established. We examined the hypothesis that anxiety and depression lead to increased plasma catecholamines and to production of reactive oxygen species (ROS) by mononuclear cells (MNC) in hypertensive individuals. We also studied the role of BP in this effect.


METHODS
In Protocol 1, a cross-sectional study was performed in 146 hypertensive patients to evaluate whether anxiety and depression affect BP and ROS formation by MNC through increasing plasma catecholamines. In Protocol 2, a 6-month randomized controlled trial using a subtherapeutic dose of the alpha(1)-adrenergic receptor antagonist doxazosin (1 mg/day) versus placebo in 86 patients with essential hypertension was performed to determine whether the increase in ROS formation by MNC was independent of BP.


RESULTS
In Protocol 1, a significant relationship was observed between the following: trait anxiety and plasma norepinephrine (r = 0.32, P < .01); plasma norepinephrine and ROS formation by MNC (r = 0.36, P < .01); and plasma norepinephrine and systolic, diastolic, and mean BP (r = 0.17, P = .04; r = 0.26, P = .02; r = 0.23, P < .01, respectively). In Protocol 2, subtherapeutic doxazosin treatment (1 mg/day) had no significant effect on BP. However doxazosin significantly decreased ROS formation by MNC compared with placebo (P < .01).


CONCLUSIONS
Trait anxiety may increase plasma norepinephrine and increase ROS formation by MNC independent of BP in hypertensive patients.
Yasunari
Kenichi
K
Department of General Medicine and Cardiology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan. yasunari@med.osaka-cu.ac.jp
Matsui
Tokuzo
T
Maeda
Kensaku
K
Nakamura
Munehiro
M
Watanabe
Takanori
T
Kiriike
Nobuo
N
D058668:Adrenergic alpha-1 Receptor Antagonists; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001007:Anxiety / Q000276:immunology / Q000378:metabolism*; D050197:Atherosclerosis / Q000097:blood / Q000276:immunology / Q000523:psychology; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003863:Depression / Q000276:immunology / Q000378:metabolism; D017292:Doxazosin / Q000008:administration & dosage; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000276:immunology* / Q000523:psychology*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D015213:Neuroimmunomodulation; D009638:Norepinephrine / Q000097:blood*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012307:Risk Factors
D058668:Adrenergic alpha-1 Receptor Antagonists; D000959:Antihypertensive Agents; D017292:Doxazosin; D006442:Glycated Hemoglobin; D008055:Lipids; D009638:Norepinephrine; D017382:Reactive Oxygen Species