Clinical and experimental studies suggest that the L-arginine-nitric oxide (NO) pathway is involved in the genesis and maintenance of arterial hypertension1,2. There are no reports confirming a direct correlation between stress and hypertension, although the cellular and molecular basis of both conditions has recently begun to be investigated1-3. We have previously demonstrated that L-arginine transport in RBCs was inhibited in hypertensive patients. The objective of this study was investigated the effect of acute stress exposure on the L-arginine-NO pathway in red blood cells (RBCs) in animal model of hypertension. RBCs were isolated from twelve 20 wk-old spontaneously hypertensive rats and twelve normotensive controls. In rat RBCs, L-arginine transport is mediated by systems y⁺ and y⁺L. In SHR, L-arginine transport (μmoles/L cells/h) via system y⁺ was not different in SHR (237 ± 31, n=6) compared to controls (242 ± 75, n=6). In contrast, transport of L-arginine by system y⁺L was significantly reduced in SHR (20 ± 8, n=6) compared to (124 ± 33, n=6). Interestingly, acute stress exposure increased impaired L-arginine uptake via system y⁺L in SHR from 20 ± 8 to 118 ± 21 (n=6). There was not any effect of acute stress on L-arginine transport in controls. The findings found here confirmed that both hypertension and stress are associated with a disturbance in the L-arginine-NO pathway. Although the association of stress and hypertension at a cellular level certainly is not simple, the results presented in this study suggest an involvement of the L-arginine-NO pathway in this link.