Introduction: Animal models of postnatal stress can be considered depression models, and many of their abnormalities are similar to those revealed in human depression^1-3. The objective of this study was to investigate the participation of vascular reactivity and the intraplatelet L-arginine-nitric oxide (NO) pathway in atherothrombosis and cardiovascular events common to depression. Methods: All experiments were reviewed and approved by the Ethics Committee of Animal Experiments of the State University of Rio de Janeiro. Eight male Wistar rats underwent a unique maternal separation (UMS) for 8 minutes at a temperature of 22°C during their second day of life; and nine control rats were included in the study. The animals were anesthethized with pentobarbital (70 mg/kg, i.p.), blood was collected by aortic puncture and the mesenteric arterial bed was rapidly removed. The reactivity of the arterial mesenteric bed was measured as described by McGregor⁴. The basal activity of intraplatelet nitric oxide synthase (NOS) was measured by the conversion of L-[³H]-arginine to L-[³H]-citrulline, and the influx of L-[³H]- arginine was evaluated during an incubation period of 5 minutes at 37°C with L-[³H]-arginine at 100 µM. Mann Whitney test was used to access the statistical significance (p<0.05). Data are presented as mean ± EP. Results: There was a difference in vasoconstriction (mmHg) caused by norepinephrine at concentrations of 1, 3 and 10 nmol in UMS rats (12 ± 2.5; 27.2 ± 3.4; 72 ± 9.6%, respectively) compared to controls rats (2.7 ± 2.6; 14.4 ± 3.9; 43.2 ± 7.5%, respectively). The vasodilator effect of acetylcholine was significantly increased in UMS rats compared to controls. In platelets, the basal activity of NOS in UMS rats (0.07 ± 0.01 pmol/10⁸ cells) was reduced compared with controls (0.17 ± 0.03 pmol/10⁸ cells.). There was also a decrease in total L-arginine transport from 0.42 ± 0.05 µmol/L/h to 0.24 ± 0.02 µmol/L/h in UMS rats. Conclusion: Our findings demonstrate that postnatal stress presents with a dysfunction of mesenteric vascular reactivity associated with an inhibition of the L-arginine-NO pathway in platelets. These results are a possible additional mechanism to understand the pathophysiology of depression and cardiovascular complications.