Vascular dysfunction associated with major depression-like symptoms: monoamine homeostasis and endothelial dysfunction

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Major depression and cardiovascular diseases have strong co-morbidity but the reason for this is unknown. In Chronic Mild Stress (CMS) model of depression only some rats develop depression-like symptoms (i.e. anhedonia, measured by sucrose intake) while others are resilient to 8 weeks of CMS. Anhedonic rats have decreased cardiac output and unchanged blood pressure, suggesting increased total peripheral resistance.
Small mesenteric and femoral arteries from CMS and non-stressed rats responded similarly to noradrenaline (NA) under control conditions but inhibition of neuronal reuptake with cocaine increased NA sensitivity stronger in anhedonic than in resilient and non-stressed groups. In contrast, corticosterone-sensitive extra-neuronal monoamine uptake was diminished in rats exposed to CMS. These changes in monoamine homeostasis were associated with upregulation neuronal NA transporter and reduced expression of extra-neuronal transporter (OCT-2) in anhedonic arteries. The contractility of middle cerebral arteries to 5-HT was reduced by CMS but recovered by anti-depressant treatment.
Resistance arteries from anhedonic rats were less sensitive to acetylcholine compared to non-stressed and resilient groups. NO-dependent relaxation and endothelial NO synthase (eNOS) were increased in arteries from anhedonic rats. Inhibition of cyclooxygenase (COX) activity revealed increased COX-2-dependent relaxation in anhedonic group. In contrast, eNOS- and COX-independent relaxation to acetylcholine (EDH-like response) was significantly reduced in anhedonic rats. This was associated with decreased transcription of intermediate-conductance Ca2+-activated K+ channels.
Our results indicate that CMS-induced depression-like symptoms in rats are associated with changes in monoamine uptake and endothelial dysfunctions in small arteries. These changes could affect peripheral resistance and organ perfusion in major depression.
Original languageEnglish
Publication year2014
Publication statusPublished - 2014
EventInternational Symposium on Resistance Arteries: ISRA - Banff, Canada
Duration: 7 Sep 201411 Sep 2014

Conference

ConferenceInternational Symposium on Resistance Arteries
CountryCanada
CityBanff
Period07/09/201411/09/2014

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