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on April 3, 2006

A more recent version of this article appeared on May 1, 2006

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Submitted on October 24, 2005
Revised on November 9, 2005

Folate Supplementation During Pregnancy Improves Offspring Cardiovascular Dysfunction Induced by Protein Restriction

Christopher Torrens; Lee Brawley; Frederick W. Anthony; Caroline S. Dance; Rebecca Dunn; Alan A. Jackson; Lucilla Poston; and Mark A. Hanson^*

From the Centre for Developmental Origins of Health and Disease (C.T., L.B., F.W.A., C.S.D., M.A.H.), University of Southampton, Princess Anne Hospital, Southampton, United Kingdom; Institute of Human Nutrition (R.D., A.A.J.), University of Southampton, Southampton General Hospital, Southampton, United Kingdom; and Division of Reproductive Health, Endocrinology, and Development (L.P.), King’s College London, London, United Kingdom.

^* To whom correspondence should be addressed. E-mail: m.hanson{at}soton.ac.uk.

Abstract--Dietary protein restriction in the rat compromises the maternal cardiovascular adaptations to pregnancy and leads to raised blood pressure and endothelial dysfunction in the offspring. In this study we have hypothesized that dietary folate supplementation of the low-protein diet will improve maternal vascular function and also restore offspring cardiovascular function. Pregnant Wistar rats were fed either a control (18% casein) or protein-restricted (9% casein) diet ±5 mg/kg folate supplement. Function of isolated maternal uterine artery and small mesenteric arteries from adult male offspring was assessed, systolic blood pressure recorded, and offspring thoracic aorta levels of endothelial nitric oxide (NO) synthase mRNA measured. In the uterine artery of late pregnancy dams, vasodilatation to vascular endothelial growth factor was attenuated in the protein-restricted group but restored with folate supplementation, as was isoprenaline-induced vasodilatation (P<0.05). In male offspring, protein restriction during pregnancy led to raised systolic blood pressure (P<0.01), impaired acetylcholine-induced vasodilatation (P<0.01), and reduced levels of endothelial NO synthase mRNA (P<0.05). Maternal folate supplementation during pregnancy prevented this elevated systolic blood pressure associated with a protein restriction diet. With folate supplementation, endothelium-dependent vasodilatation and endothelial NO synthase mRNA levels were not significantly different from either the control or protein-restricted groups. Maternal folate supplementation of the control diet had no effect on blood pressure or vasodilatation. This study supports the hypothesis that folate status in pregnancy can influence fetal development and, thus, the risks of cardiovascular disease in the next generation. The concept of developmental origins of adult disease focuses predominately on fetal life but must also include a role for maternal cardiovascular function.

Key words: diet • endothelium • hypertension, experimental • nitric oxide • pregnancy

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