The pre- and post-natal nutrient environments are implicated in the development of cardiovascular disease in later life (Eriksson et al. 2001). In sheep, undernutrition in early gestation alters fetal peripheral vascular reactivity (Ozaki et al. 2000; Nishina et al. 2003) and cardiovascular control in fetal and early postnatal life (Hawkins et al. 2000). However, to date, there is little information in sheep on the effect of diet in early gestation on vascular function in adulthood or how this is affected by postnatal nutrition. Pregnant Welsh Mountain ewes (Animals (Scientific Procedures) Act 1986) received either 100% nutrient requirements throughout gestation (control C, n=13) or a 50% total reduction in total nutrient intake for 30 days post conception, and 100% nutrient requirements thereafter (Restricted, U, n=12). At weaning, a subset of the offspring from each group were fed ad libitum (CC, n=5 & UC, n= 5) or a restricted diet (CU, n=8 & UU, n=7) to reduce body weight to 85% of individual target weight (predicted from 0 – 12 week growth trajectory) between 12 and 25 weeks, and ad libitum thereafter. At 2.5 years of age sheep were killed humanely with sodium pentobarbitone (160 mg/kg i.v.) and third order mesenteric arteries were dissected and mounted on a wire myograph bathed in PSS gassed with 95% O2 and 5% CO2 at 37 °C. Following normalisation, cumulative concentration-response curves to phenylephrine (10 nM to 10 μM), endothelin (1 pM to 10 nM), acetylcholine (1 nM to 100 μM), bradykinin (1 pM to 1 μM) and adenosine (1 pM to 100 μM) were constructed. Data are presented as mean ± S.E.M. and were analysed by ANOVA with Bonferroni post-hoc correction for multiple comparisons. Significance was accepted for P<0.05. Comparison of sigmoidal curves fitted to the data demonstrated that vasodilatation to acetylcholine (UC & UU: n=14) and adenosine (UC & UU: n=7) was significantly impaired in sheep exposed to the pre-natal challenge (UC & UU, n=12) compared to the control (CC & CU: n=13 & n=7, respectively) (P<0.05), regardless of postnatal nutrition. Vasodilatation to bradykinin (UC & UU: n=14) was significantly enhanced in sheep exposed to the pre-natal challenge compared to the control (CC & CU: n=10) (P<0.05). Conversely, vasoconstriction to phenylephrine was significantly enhanced in sheep exposed to a post-natal challenge (CU & UU: n=11) compared to control (CC & UC: n=14) (P<0.05), regardless of prenatal nutrition. There was no difference between groups in the response to endothelin. This study shows that the nutrient environment in early development has effects on mesenteric vascular reactivity in adult life. Our findings suggest that vasodilator (endothelium-dependent and -independent) and vasoconstrictor (i.e. sympathetic) vascular control mechanisms are differentially perturbed by pre- and post-natal nutrient challenges.
- Microvascular & Endothelial and Placental & Perinatal Physiology (Joint Session) C83-C88 PC107-PC120
University of Bristol (2005) J Physiol 567P, C83
Oral Communications: The effect of moderate maternal postconceptional undernutrition and undernutrition in early postnatal life on mesenteric vascular reactivity in adult sheep
Snelling, Tristram Henry; Torrens, Christopher; Noakes, David E.; Poston, Lucilla; Boullin, Julian P.; Khan, Omar A.; Ohri, Sunil K.; Green, Lucy R.; Hanson, Mark A.;
1. Centre for Developmental Origins of Health and Disease, University of Southampton, Southampton, United Kingdom. 2. Division of Reproductive Health, Endocrinology and Development, Kings College London , London, United Kingdom. 3. Department of Veterinary Reproduction, Royal Veterinary College, London, United Kingdom. 4. Wessex Cardiothoracic Unit, Southampton General Hospital, Southampton, United Kingdom.
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