Proceedings of The Physiological Society

Physiology 2015 (Cardiff, UK) (2015) Proc Physiol Soc 34, PC130

Poster Communications

Vitamin D deficient diet in pregnancy alters isolated femoral vasodilatation in the late gestation fetal sheep

C. Torrens1, M. Fayyaz1, L. Mercken1, C. Cooper2, N. C. Harvey2, R. O. Oreffo1, P. C. Calder1, M. A. Hanson1, K. R. Poore1, L. R. Green1

1. Institute of Developmental Sciences, University of Southampton, Southampton, Hants, United Kingdom. 2. MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom.

Vitamin D deficiency is linked to cardiovascular disease in adults, involving vascular smooth muscle and endothelial cells which express the vitamin D receptor (1). Substantial portions of the human population, including pregnant women, have circulating vitamin D levels at the lower end of the measurable range (2) which is important since the fetus is dependent on the mother for supply of vitamin D. Restriction of dietary vitamin D during pregnancy and lactation leads to endothelial dysfunction in young postnatal rat offspring (3). However while previous studies have shown that undernutrition in gestation leads to cardiovascular adaptations in the fetus (4, 5), there is a paucity of information linking specifically maternal vitamin D status to fetal cardiovascular function. Welsh mountain ewes were fed 100% nutrient requirements (C, 2000 IU/kg vitamin D, n= 7), or a similar diet depleted in vitamin D3 (VDD, 0 IU/kg vitamin D, n=9) from 17 days prior to conception until post-mortem. At 126-130 days of gestation ewes and fetuses were killed (pentobarbitone overdose IV). Small (~250 µm) second- or third-order fetal femoral arteries were dissected and mounted on a wire myograph in physiological salt solution (37°C with 95% O2 and 5% CO2). In vessels preconstricted with U46619 (a thromboxane mimetic), endothelium-dependent relaxation was determined using carbachol (CCh, 0.1 nM-10 µM) and endothelium-independent relaxation using the NO donor, sodium nitroprusside (SNP, 0.1 nM-10 µM). Data are expressed as mean ± SEM and were analysed by t-test. Significance was accepted when p<0.05. Femoral endothelium-dependent vasodilatation was blunted in VDD compared to control group fetuses (pEC50 C, 6.55 2 ± 0.19, n=7; VDD, 5.79 ± 0.09, n=9; p<0.05), with no effect on maximal response. In contrast, femoral endothelium-independent vasorelaxation response to SNP was enhanced in VDD compared to control group fetuses (pEC50: C, 6.27 ± 0.47. n=5; VDD, 8.031 ± 0.23, n=8; p<0.01), with no effect on maximal response. Our data suggest that in pregnancies of reduced dietary vitamin D there is a disruption in the contribution of endothelial and smooth muscle mechanisms in the regulation of fetal femoral artery tone. This could involve altered expression of endothelial nitric oxide synthase or smooth muscle guanylate cyclase (1). Such adaptations in vascular control may impact on fetal hind limb blood flow and muscle growth, and have additional ramifications for adult cardiovascular and metabolic health.

Where applicable, experiments conform with Society ethical requirements