Association Between Endothelial Dysfunction and Depression-Like Symptoms in Chronic Mild Stress Model of Depression

Bibliographic Data

ID19306989
AuthorsElena V Bouzinova (0000-0001-9511-8009, Aarhus University), Rikke Norregaard (0000-0002-0580-373X, Aarhus University), Donna M B Boedtkjer, Donna Briggs Boedtkjer (0000-0003-1736-3484, Aarhus University Hospital), Irina A Razgovorova (0000-0003-4520-590X, Committee on Publication Ethics), Anaïs M J Moeller (Aarhus University), Olga Kudryavtseva (0000-0003-3945-0159, Aarhus University Hospital), Ove Wiborg (0000-0002-0555-2811, Committee on Publication Ethics), Christian Aalkjaer (0000-0003-2618-4015, Committee on Publication Ethics), Vladimir V Matchkov (0000-0002-3303-1095, Aarhus University Hospital, corresponding author)
Year2014
Volume76
Issue4
Pages268-276
Publication date2014-05-01
Open AccessNo
TypeARTICLE
VenuePsychosomatic Medicine (JOURNAL)
Journal identifiersISSN: 0033-3174 • E-ISSN: 1534-7796
PublisherOvid Technologies (Wolters Kluwer Health) (PUBLISHER)
DOI10.1097/psy.0000000000000062
PMID24804883
OpenAlexW1994012475
LanguageEN
Citations received1
References cited47

OBJECTIVE: Cardiovascular diseases have high comorbidity with major depression. Endothelial dysfunction may explain the adverse cardiovascular outcome in depression; therefore, we analyzed it in vitro. In the chronic mild stress model, some rats develop depression-like symptoms (including "anhedonia"), whereas others are stress resilient. METHODS: After 8 weeks of chronic mild stress, anhedonic rats reduced their sucrose intake by 55% (7%), whereas resilient rats did not. Acetylcholine-induced endothelium-dependent relaxation of norepinephrine-preconstricted mesenteric arteries was analyzed in nonstressed, anhedonic, and resilient rat groups. RESULTS: Small resistance arteries from anhedonic rats were less sensitive to acetylcholine than those of the nonstressed and resilient groups (p = .029). Pathways of endothelium-dependent relaxation were altered in arteries from anhedonic rats. Nitric oxide (NO)-dependent relaxation and endothelial NO synthase expression were increased in arteries from anhedonic rats (0.235 [0.039] arbitrary units and 155.7% [8.15%]) compared with the nonstressed (0.135 [0.012] arbitrary units and 100.0% [8.08%]) and resilient (0.152 [0.018] arbitrary units and 108.1% [11.65%]) groups (p < .001 and p = .002, respectively). Inhibition of cyclooxygenase (COX) activity revealed increased COX-2-dependent relaxation in the anhedonic group. In contrast, endothelial NO synthase- and COX-independent relaxation to acetylcholine (endothelium-dependent hyperpolarization-like response) was reduced in anhedonic rats (p < .001). This was associated with decreased transcription of intermediate-conductance Ca-activated K channels. CONCLUSIONS: Our findings demonstrate that depression-like symptoms are associated with reduced endothelium-dependent relaxation due to suppressed endothelium-dependent hyperpolarization-like relaxation despite up-regulation of the NO and COX-2-dependent pathways in rat mesenteric arteries. These changes could affect peripheral resistance and organ perfusion in major depression

Anxiety · Association (psychology) · Chronic stress · Depression (economics) · Depressive symptoms · Endothelial Dysfunction · Psychiatry · Psychotherapist · Stress (linguistics) · Clinical Psychology · Internal Medicine · Medicine · Nitric Oxide and Endothelin Effects · Philosophy · Psychology · Stress Responses and Cortisol · Tryptophan and brain disorders

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