Maternal protein restriction in the rat impairs resistance artery but not conduit artery function in pregnant offspring

Abstract

Dietary protein restriction during gestation has been shown to produce vascular dysfunction in pregnant rats and hypertension in their offspring. However, no studies have to date examined the effects of such 'programming' on the vascular function of female offspring when they in turn become pregnant. We have therefore studied isolated conduit and resistance artery function from pregnant female offspring of control (C, 18 % casein) and protein-restricted (PR, 9 % casein) pregnant dams. There were no differences in birth weight, weight gain during pregnancy, litter size, fetal weight, placental weight, fetal : placental weight ratio or organ weights between the C and PR groups. In isolated mesenteric arteries, the vasodilatation in response to the endothelial-dependent vasodilator acetylcholine (ACh) and the beta-adrenoceptor agonist isoprenaline was decreased in the PR group, while there were no differences in the constriction in response to potassium (125 mM) or the alpha1-adrenoceptor agonist phenylephrine (PE). No differences in any responses were seen in the isolated thoracic aorta. We conclude that dietary protein restriction in pregnancy programmes vasodilator dysfunction in isolated resistance arteries of female offspring when they become pregnant, but does not affect conduit arteries.

Effects of Oxidative Stress on Vascular Reactivity in the Offspring of Protein-Restricted Stroke-Prone Spontaneously Hypertensive Rats

“…We also found that AChinduced relaxation, but not PE-induced contraction, was lower in the PR group. Similar results have beene reported by Torrens et al, 18) although Sathishkumar et al 19) have reported that prenatal protein restriction increased the expression of the vascular angiotensin II type 1 receptor and the angiotensin II-induced vasoconstriction. These results indicate that a protein restriction in pregnant rats affected the vascular reactivity of their offspring.…”

Protein Restriction during Pregnancy Induces Hypertension and Impairs Endothelium-Dependent Vascular Function in Adult Female Offspring

“…These human studies are strongly supported by animal experiments showing that a severe but balanced limitation of fetal substrate supply retards fetal growth and induces CV dysfunction and hypertension [7,8,9,10]. The hypothesis of developmental origins of disease proposes that maternal undernutrition causes permanent changes in structure and function of tissues and organs, resulting in CV and related disorders in the offspring [11, 12].…”

“…Previous studies on dietary restriction produced variable results on birth weight. In some investigations, birth weight was reduced [34, 35], in others unchanged [7, 10, 14, 36] and in some even increased [37]. The discrepancies may be due to factorsthat may alter response of the mother and fetus to nutrientrestriction such as strain, maternal age and differencesin the diets.…”

“…The mechanisms involved in the programming of adult hypertension have remained unknown, although a significant correlation between adverse intrauterine environments and alterations of vascular or endothelial function has been reported [10, 13, 14]. In addition, a possible role for the renin-angiotensin system [15, 16], the kidney [17, 18] and stress-induced stimulation of the hypothalamic-pituitary-adrenal axis [19,20,21] has been identified.…”

The Effect of Maternal Macronutrient Intake on Phenotype Induction and Epigenetic Gene Regulation

“…Feeding a PR diet to pregnant rats in the F 0 generation resulted in elevated blood pressure and endothelial dysfunction (Torrens et al, 2003) in both the F 1 and F 2 generations, despite normal nutrition during pregnancy in the F 1 generation. Hypomethylation of the hepatic GR and PPAR␣ promoters was also observed in both the F 1 and F 2 male offspring (Burdge et al, 2007b), suggesting that transmission of a phenotype induced in the F 1 generation to the F 2 generation may involve preservation of induced changes in the methylation of specific genes.…”