Impaired endothelial-dependent vasodilatation in old but not young female offspring of rats fed a protein restriction diet during pregnancy

University College London 2006 (2006) Proc Physiol Soc 3, C111

Oral Communications: Impaired endothelial-dependent vasodilatation in old but not young female offspring of rats fed a protein restriction diet during pregnancy

Christopher Torrens1, Joanne L Rodford1, Timothy Wheeler1, Mark A Hanson1, Geraldine F Clough1

1. Centre for Developmental Origins of Health & Disease, School of Medicine, University of Southampton, Southampton, United Kingdom.

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In the rat, the restriction of dietary protein during pregnancy leads to raised blood pressure and impaired endothelium-dependent vasodilatation in the male offspring (Brawley et al. 2003). Ageing is known to impair endothelium-dependent vasodilatation along with a number of other effects on the vasculature (Atkinson et al. 1994), and may be especially important in postmenopausal women, given the cardioprotective associations of oestrogen (Barrett-Connor, 1997). The present study investigated the effects of protein restriction in utero on vascular function in female offspring during oestrus at and post-cessation of the oestrus cycle. Pregnant Wistar rats were fed either a control diet (C; 18% casein) or a protein-restricted diet (PR; 9% casein) throughout gestation from conception. Small mesenteric arteries (~250 μm) of female offspring at 17 weeks (n=4-6, in oestrus) and 56 weeks (n=5-6, post oestrus cycle), were dissected and mounted in the wire myograph. Segments were bathed in physiological salt solution, at 37°C and continually gassed with 95% O2 and 5% CO2. Following normalisation, cumulative concentration response curves were constructed to phenylephrine (PE; 10 nM-100 μM) and the endothelium-dependent vasodilator acetylcholine (ACh; 1 nM-10 μM). Data are presented as mean ± SEM and differences calculated by two-way ANOVA. Significance was accepted for p<0.05. Vasoconstriction to PE did not differ between C and PR offspring at either age (p=ns), but constriction to PE did decrease with age (two-way ANOVA, p<0.05). Similarly, endothelial function as assessed by ACh was significantly blunted with ageing in both C and PR offspring (pEC50: C, young, 7.59 ± 0.16, n=6; old, 7.06 ± 0.24, n=4; % max response: PR, young, 78.5 ± 4.2, n=5; old 26.3 ± 12.0, n=6; two-way ANOVA, p<0.01). The extent of the blunting with age seen in the PR group was considerably larger than that seen in the controls and unmasked a significant difference in response between the C and PR groups in the older animals (two-way ANOVA, p<0.05), which was not present at the 17 week timepoint (p=ns). These data demonstrate that the vascular effects of protein restriction in utero seen in young female offspring are less apparent than in the male offspring (Brawley et al. 2003), during pregnancy (Torrens et al. 2003) or after the cessation of the oestrus cycle. This suggests a protective role of oestrogen in the vasculature of young female rats, which masks an underlying defect apparent in old age or during a metabolic challenge in pregnancy.



Where applicable, experiments conform with Society ethical requirements.

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