Institut for Biomedicin

Christian Aalkjær

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

Publikation: KonferencebidragKonferenceabstrakt til konferenceForskningpeer review

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.
StatusUdgivet - 2014
BegivenhedInternational Symposium on Resistance Arteries: ISRA - Banff, Canada
Varighed: 7 sep. 201411 sep. 2014


KonferenceInternational Symposium on Resistance Arteries

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