Vascular dysfunction in Chronic Mild Stress (CMS) induced depression model in rats: 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 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 antidepressant treatment. Resistance arteries from anhedonic rats were less sensitive to acetylcholine compared to nonstressed 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 COXindependent 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 yearAug 2014
Number of pages1
Publication statusPublished - Aug 2014
EventPharmacology and Physiology: International Scientific Congress 2014: Pharmacology and Physiology - Putra World Trade Centre, Kuala Lumpur, Malaysia
Duration: 22 Aug 201424 Aug 2014

Conference

ConferencePharmacology and Physiology: International Scientific Congress 2014
LocationPutra World Trade Centre
CountryMalaysia
CityKuala Lumpur
Period22/08/201424/08/2014

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