A number of studies in rats have assessed the reactivity of isolated vessels from the offspring of globally dietary restricted dams (Holemans et al. 1999; Ozaki et al. 2001). Endothelium-dependent dilator responses were reduced in mesenteric (Holemans et al. 1999) and femoral (Ozaki et al. 2001) arteries in these nutritional models. Dietary protein restriction of pregnant rats resulted in their offspring developing hypertension (Langley & Jackson, 1994). However, no studies have investigated the vascular function of offspring using this nutritional model. Therefore, the aim of the study was to assess isolated resistance artery function from male offspring of control and protein-restricted dams.

All procedures were carried out according to UK legislation. Female Wistar rats were fed either a control (18 % casein) or a low protein (9 % casein) diet throughout pregnancy. At term, the experimental rat diet (18/9 % casein) was replaced with standard laboratory chow. Male offspring of control (C) and protein-restricted (PR) dams were fed standard chow until 87 ± 1 days of age, when 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 conducted. Endothelium-dependent relaxation was assessed by acetylcholine (ACh)-(1 nM-10 µM) and bradykinin (BK) (1-10 µM)-induced relaxation in PE (EC₈₀) pre-constricted arteries. Endothelium-independent relaxation was determined by sodium nitroprusside (SNP)-induced relaxation (0.1 nM-30 µM). Data are expressed as means ± S.E.M. of 7-9 observations and differences between groups are determined by Student’s t test and two-way ANOVA. Relaxation induced by endothelium-dependent vasodilators, ACh (-log EC₅₀: C, 7.58 ± 0.05, n = 8; PR, 6.88 ± 0.07, n = 9, P < 0.001) or BK (% maximum relaxation : C, 71 ± 6, n = 7; PR, 33 ± 7, n = 9, P < 0.01) was significantly reduced in the PR group. Sensitivity to SNP was lowered in the PR offspring compared with C (n = 7-9, P < 0.001, two-way analysis of variance).

In conclusion, dietary protein restriction in pregnancy programmes the development of attenuated vasorelaxation in male offspring. Impairment of vascular smooth muscle sensitivity to nitric oxide may contribute to the observed defect in relaxation to the endothelium-dependent dilator, acetylcholine.

This work was supported by the British Heart Foundation.