Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 309, Issue 8, Pages R814-R823Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00337.2014
Keywords
depression; chronic mild stress; escitalopram; endothelium; nitric oxide synthase; cyclooxygenase; endothelium-derived hyperpolarization; oxidative stress; glutathione; malondialdehyde
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Funding
- Danish Heart Foundation
- A. P. Moller and his wife C. Mc-Kinney-Moller Foundation for Medical Science Promotion
- Lundbeck Foundation
- Saint-Petersburg State University Research Grant [1.0.133.2010]
- Lundbeck Foundation [R118-2012-11567, R44-2009-4153] Funding Source: researchfish
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Major depression is known to be associated with cardiovascular abnormalities, and oxidative stress has been suggested to play a role. We tested the hypothesis that antidepressant treatment reduces oxidative stress and endothelial dysfunctions in the chronic mild stress (CMS) model of depression in rats. Rats with >30% reduction in sucrose intake after 4 wk of CMS were defined in the study as CMS-susceptible and compared with unstressed controls. Sixteen CMS-susceptible and eight unstressed rats were treated during weeks 5 to 8 of the CMS protocol with escitalopram. Escitalopram-treated rats with >20% recovery in the sucrose consumption during the last 2 wk of treatment were defined as escitalopram responders. Rats that did not reach these criteria were defined as escitalopram nonresponders. In the open field test, escitalopram responders demonstrated anxiolytic effect of treatment. In mesenteric small arteries, escitalopram affected neither NO nor cyclooxygenase-1 (COX-1)-mediated vasodilation. Escitalopram potentiated endothelium-dependent hyperpolarization-like response, which was suppressed in the vehicle-treated CMS-susceptible rats and reduced COX-2-dependent relaxation, which was elevated in the vehicle-treated CMS-susceptible rats. Escitalopram did not affect blood pressure and heart rate, which were elevated in the vehicle-treated CMS-susceptible rats. Oxidative stress markers were changed in association with CMS in liver, heart, and brain. Escitalopram normalized oxidative stress markers in the majority of tissues. This study demonstrates that the antidepressant effect of escitalopram is associated with partial improvement of endothelial function in small arteries affecting COX-2 and endothelium-dependent hyperpolarization-like pathways.
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