Epidemiological studies demonstrate that low birth weight is associated with an increased risk of cardiovascular disease in adult life (Osmond et al., 1993). In the rat, the restriction of dietary protein during gestation leads to raised systolic blood pressure and endothelial dysfunction in the offspring (Langley & Jackson, 1994; Brawley et al., 2003). Yet whilst blood pressure has been shown to be elevated by 4 weeks of age, endothelial function has not been assessed before 80 days (Brawley et al., 2003). The aim of the present study was to determine if endothelial dysfunction was present with the onset of raised blood pressure. Pregnant Wistar rats were fed a control (C; 18% casein) or protein restricted (PR; 9% casein) diet throughout pregnancy and returned to standard chow postpartum. Pups were weaned from their mothers at 21 days. At approximately 36 days blood pressure in male offspring was recorded using tail cuff plethysmography, before animals were sacrificed and thoracic aorta dissected and mounted in a wire myograph. Aorta segments were bathed in PSS heated to 37° C and continually gassed with 95% O₂ and 5% CO₂. Concentration response curves were conducted to phenylephrine (PE), the thromboxane mimetic U46619, acetylcholine (ACh), bradykinin (BK) and sodium nitroprusside (SNP). Responses to ACh were repeated in the presence of L-NAME (100 µM). Data is given as mean ± S.E.M. and differences were assessed by one-way ANOVA with Bonferroni post hoc correction. Significance was accepted at p<0.05. Blood pressure at 5 weeks was similar between the groups (mmHg: C, 86.61 ± 4.15, n=9; PR, 88.50 ± 6.18, n=8; p=ns). Contractile responses to PE were similar between the groups, yet vasoconstriction to U46619 was significantly enhanced in the PR group compared to controls (pEC₅₀: C, 7.67 ± 0.05, n=7; PR, 8.01 ± 0.05, n=6, p<0.01). Endothelial-dependent vasodilatation to both ACh (pEC₅₀: C, 7.82 ± 0.10, n=7; PR, 7.52 ± 0.07, n=6; p<0.05) and BK (% max response: C, 29.2 ± 4.5, n=6; PR, 9.0 ± 3.4, n=5; p<0.01) was significantly impaired in the PR group compared to controls. Incubation with L-NAME completely abolished the ACh response in all groups and responses to the NO-donor SNP were similar in both groups (p=ns). The data demonstrates that protein restriction during gestation leads to vascular dysfunction in isolated thoracic aorta segments, which is present from 5 weeks of age and is independent of any increase in blood pressure.