Maternal undernutrition in rat pregnancy induces vascular dysfunction in isolated arteries of their offspring, which are more pronounced in the male (Ozaki et al. 2001). Conversely, high fat during gestation resulted in elevated systolic blood pressure in female adult rat offspring only (Khan et al. 2002). We have previously shown endothelium-dependent relaxation is impaired in isolated resistance arteries from male rats exposed to maternal low protein diet in utero (Brawley et al. 2002). This study investigates vascular function of female offspring using the low protein model and compares isolated resistance artery function from female and male adult offspring of control and protein-restricted dams.

Female Wistar rats were fed either a control (C, 18 % casein) or low protein (PR, 9 % casein) diet throughout pregnancy. Both diets were replaced with standard laboratory chow at term. Male (M-C, M-PR) and female (F-C, F-PR) offspring of C and PR dams were fed standard chow until 130 ± 5 days of age. They were humanely killed by CO₂ inhalation and cervical dislocation. Small mesenteric arteries (internal diameter ~300 µm) were mounted on a wire myograph. Phenylephrine (PE) (10 nM– 100 µM) concentration-response curves were constructed. Endothelium-dependent relaxation was assessed by acetylcholine (ACh, 1 nM-10 µM)-induced relaxation in PE (EC₈₀) pre-constricted arteries. Data are expressed as means ± S.E.M. of 7-8 observations. Differences between groups are determined by Student’s unpaired t test and ANOVA.

PE-induced vasoconstriction was not different between dietary groups or genders (% maximum constriction: M-C, 106 ± 3; M-PR, 109 ± 2; F-C, 110 ± 3; F-PR, 113 ± 2, n = 7-8, P > 0.05). In male offspring, relaxation induced by ACh was significantly shifted to the right in the PR group (-log EC₅₀: M-C, 7.80 ± 0.02, n = 7; M-PR, 7.32 ± 0.03, n = 8, P < 0.001) with no change in maximum relaxation. In females, the maximum relaxation induced by ACh was significantly attenuated in the PR group compared with the C group (% maximum relaxation: F-C, 88 ± 2; F-PR, 44 ± 12, n = 8, P < 0.01). Moreover, the maximum ACh responses of the M-PR and F-PR were significantly different (% maximum relaxation: M-PR, 92 ± 4, n = 8, P < 0.01).

Dietary protein restriction in pregnancy programmes development of attenuated endothelium-dependant vasorelaxation in female and male offspring. These vascular defects appear to be gender-related with effects being more pronounced in PR-F offspring.

This work was supported by the BHF.