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Psychosom Med. 2014 May;76(4):268-76. doi: 10.1097/PSY.0000000000000062.

Association between endothelial dysfunction and depression-like symptoms in chronic mild stress model of depression.

Author information

1
From the Department of Clinical Medicine (E.V.B., R.N., O.W.), Aarhus University Hospital, Aarhus, Denmark; Department of Biomedicine (D.M.B.B., A.M.J.M., O.K., C.A.,V.V.M), MEMBRANES, Aarhus University, Aarhus, Denmark; and Department of General Physiology (I.A.R.), St Petersburg State University, St Petersburg, Russia.

Abstract

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.

PMID:
24804883
DOI:
10.1097/PSY.0000000000000062
[Indexed for MEDLINE]

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