Maternal separation (MatSep) is a model of behavioral stress during early life in rodents. This model of early life stress has been extensively studied with respect to behavioral outcomes in adulthood. MatSep induces a pro-anxiety phenotype in adult rats. We hypothesized that MatSep may also promote vascular dysfunction and/or overt cardiovascular disease. MatSep was performed in male Wistar Kyoto rats 3 hs/day from day 2 to 14 of life. Non-separated littermate rats (NS) were used as control. For all experiments described with ex vivo tissues, we utilized intraperitoneal injection of 65mg/kg sodium pentobarbital to terminate the rats for dissection of tissues. We reported that MatSep induces an exaggerated angiotensin II (AngII)-induced aortic constriction ex vivo in adult male rats. The exaggerated AngII-mediated aortic constriction was specific to the AngII pathway because other vasoconstrictor mediators (ET-1, phenylephrine, KCl) did not elicit an exaggerated response in the MatSep rats. We found that MatSep induces a dysfunction in AngII-mediated signaling specifically in the endothelium, such that NOS activation was impaired and NO buffering was reduced. AngII receptors, AT1 and AT2, function was determined. Vascular AT2 activation was impaired, while AT1 appeared to be intact. Moreover, vascular AT2 expression was significantly reduced. AT1 receptor and other known AngII pathway genes were shown to have similar expression levels in MatSep and NS rats. We hypothesized that MatSep would induce an AngII-sensitive phenotype in vivo. We anesthetized rats with 2% isoflurane gas by inhalation and inserted radiotelemetry devices to monitor blood pressure chronically. In vivo, MatSep rats elicit exacerbated AngII-induced hypertension mediated via a loss of NO buffering capacity as elucidated with L-NAME (NOS inhibitor) in the drinking water. AngII infusion induced a significant increase in AT1 receptor expression in the renal cortex of MatSep rats, while in NS rats a decrease in AT1 receptor expression was found. AngII infusion in the MatSep rats enhanced increased T cell and macrophage infiltration to the endothelium and the peri-vascular adventitia of the aorta; as well as T cell infiltration was shown to be exaggerated in the renal cortex by immunohistochemical techniques. Remarkably, AngII-induced renal damage was exaggerated exclusively in the interstitial arteries of MatSep rats by histological analyses. These data indicate that MatSep sensitizes AngII responses via increased activation of AT1 receptors, leading to an increased hemodynamic response associated with an enhanced T cell activation. To further elucidate the immune response of the MatSep rats, we exposed NS and MatSep rats to an acute (12 hr) exposure of lipopolysaccharide (LPS) injected intraperitoneally. No differences were found in the number of circulating or renal T cells at baseline or in LPS-treated rats. Renal tissue from LPS-treated MatSep rats showed a 4 to 16 fold increase in levels of cytokines (IL-16, CCL3, CCL4, IFNg), chemokine receptors (CCR3, CCR4, CXCR4) and activation markers (CD40, CD40Ig) compared to LPS-treated NS rats indicating that MatSep sensitizes T cell activation. These results indicate that MatSep enhances pro-inflammatory activation of circulating and renal T cells, which most likely leads to promotion of pathological cardiovascular responses. Our findings provide new insights in the mechanisms of developmental programming of cardiovascular disease and new risk factors associated to an adverse postnatal environment.