Vladimir Matchkov

TY - ABST

T1 - Vascular dysfunction associated with major depression-like symptoms: monoamine homeostasis and endothelial dysfunction

AU - Bouzinova, Elena

AU - Andresen, Jørgen

AU - Wiborg, Ove

AU - Aalkjær, Christian

AU - Matchkov, Vladimir

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

M3 - Conference abstract for conference

T2 - International Symposium on Resistance Arteries

Y2 - 7 September 2014 through 11 September 2014

ER -