Depression and cardiovascular disease are known to occur simultaneously but the reason for this association is unknown. Elevated total peripheral resistance, which is often seen in cardiovascular diseases, has recently been shown to be associated with depression. The reason for this is unclear. We have studied the functional and structural changes isolated resistance arteries from male Wistar rats associated with stress induced depression. Three different types of resistance arteries were studied under isometric conditions: middle cerebral (CA), femoral (FA) and mesenteric small arteries (MSA). The rat model of chronic mild stress (CMS) induced depression was used. Rats were subjected to CMS for 8 weeks and tested for the major depression symptom, anhedonia, i.e. an inability to experience pleasure from normally pleasurable stimuli. Only some of the rats developed anhedonia (evidenced by reduced sugar intake), while others were stress-resistant (resilient). We did not find any significant changes in artery structure. MSA from all three groups (anhedonic, resilient and non-stressed controls) responded similarly to noradrenaline (NA) but cocaine unmasked an elevated NA sensitivity of MSA from anhedonic rats. This was also seen in FA but the effect of cocaine was less pronounced. FA from anhedonic rats showed increased maximal tension to NA in comparison to the control and resilient groups. CA from anhedonic rats showed increased maximal tension and were more sensitive to 5-HT in comparison to the control groups. Our results correlated with changes in corticosterone which transiently increased to stress and the transient lasted longer in the depressed rats. Thus, our results indicate that depression-like symptoms are associated with increase in the contractility and agonist sensitivity of resistance arteries. In innervated arteries this can be masked by elevated neuronal reuptake. These changes might be important for the cardiovascular events associated with depression.