OBJECTIVE: Previous studies in humans and animals have suggested that undernutrition in utero and in early post-natal life may lead to altered vascular function in a number of peripheral arteries. We investigated the effect of pre- and post-natal nutrient restriction on the vascular reactivity of the left internal thoracic artery using a sheep model. METHODS: Welsh mountain ewes were mated and assigned to three dietary groups: (1) 100% of total nutritional requirements (control, n=6); (2) 50% of total nutritional requirements during the first 31 days of gestation (n=6); and (3) 50% nutritional restriction during the first 31 days of gestation, followed by a restriction in the diet of their offspring 12-25 weeks post-natally, designed to produce a 15% reduction in growth trajectory (n=7). The male offspring were sacrificed at 130 weeks; the left internal thoracic artery was mounted onto a wire myograph and the reactivity of the vessel to various agonists measured. RESULTS: The offspring of animals who underwent an early gestation nutrient restriction had a significantly increased basal tone (0.41+/-0.25 vs 6.34+/-1.35, p=0.015) and sensitivity to phenylephrine (log EC(50): -6.23+/-0.04 M vs -5.74+/-0.17 M, p=0.036) as compared with control animals. However, this phenomenon was not seen in animals that underwent both pre- and post-natal nutrient restriction. CONCLUSIONS: Pre-natal undernutrition increases the basal tone and sensitivity of the left internal thoracic artery to phenylephrine. This effect is significantly attenuated by continued undernutrition in early post-natal life. These experiments suggest that in utero and early post-natal undernutrition may be important determinants of graft function in later life.
OBJECTIVE: Previous studies in humans and animals have suggested that undernutrition in utero and in early post-natal life may lead to altered vascular function in a number of peripheral arteries. We investigated the effect of pre- and post-natal nutrient restriction on the vascular reactivity of the left internal thoracic artery using a sheep model. METHODS: Welsh mountain ewes were mated and assigned to three dietary groups: (1) 100% of total nutritional requirements (control, n=6); (2) 50% of total nutritional requirements during the first 31 days of gestation (n=6); and (3) 50% nutritional restriction during the first 31 days of gestation, followed by a restriction in the diet of their offspring 12-25 weeks post-natally, designed to produce a 15% reduction in growth trajectory (n=7). The male offspring were sacrificed at 130 weeks; the left internal thoracic artery was mounted onto a wire myograph and the reactivity of the vessel to various agonists measured. RESULTS: The offspring of animals who underwent an early gestation nutrient restriction had a significantly increased basal tone (0.41+/-0.25 vs 6.34+/-1.35, p=0.015) and sensitivity to phenylephrine (log EC(50): -6.23+/-0.04 M vs -5.74+/-0.17 M, p=0.036) as compared with control animals. However, this phenomenon was not seen in animals that underwent both pre- and post-natal nutrient restriction. CONCLUSIONS: Pre-natal undernutrition increases the basal tone and sensitivity of the left internal thoracic artery to phenylephrine. This effect is significantly attenuated by continued undernutrition in early post-natal life. These experiments suggest that in utero and early post-natal undernutrition may be important determinants of graft function in later life.
Authors: Jane K Cleal; Kirsten R Poore; Julian P Boullin; Omar Khan; Ryan Chau; Oliver Hambidge; Christopher Torrens; James P Newman; Lucilla Poston; David E Noakes; Mark A Hanson; Lucy R Green Journal: Proc Natl Acad Sci U S A Date: 2007-05-04 Impact factor: 11.205
Authors: Katharine C Pike; Shelley A Davis; Samuel A Collins; Jane S A Lucas; Hazel M Inskip; Susan J Wilson; Elin R Thomas; Harris A Wain; Piia H M Keskiväli-Bond; Cyrus Cooper; Keith M Godfrey; Christopher Torrens; Graham Roberts; John W Holloway Journal: Sci Rep Date: 2014-04-17 Impact factor: 4.379