Glycine rectifies vascular dysfunction induced by dietary protein imbalance during pregnancy

Abstract

Protein restriction in rat pregnancy programmes the development of elevated systolic blood pressure and vascular dysfunction in the offspring. A recent study has shown that hypertension is reversed by maternal glycine supplementation. Whether this protective effect is exerted directly on the embryo and fetus, or indirectly via effects on the mother, is unknown although we have previously shown abnormalities in the maternal vasculature. We tested the hypothesis that dietary glycine repletion would reverse endothelial dysfunction in protein-restricted pregnant rat dams using wire myography. Impaired acetylcholine-(P < 0.01) and isoprenaline-induced (P < 0.05) vasodilatation in isolated mesenteric arteries (MA) from protein-restricted pregnant dams was accompanied by reduced vascular nitric oxide (NO) release (P < 0.05). Dietary glycine supplementation reversed vascular dysfunction in MA (P < 0.05) and improved NO release thus potentially protecting the maternal circulation. The impaired NO release in the MA of low protein diet dams was not accompanied by reduced eNOS mRNA expression, suggesting that eNOS activity was altered. Protein restriction did not alter the vascular function of a conduit artery, the thoracic aorta. These results provide evidence that adequate provision of glycine, a conditionally essential amino acid in pregnancy, may play a role in the vascular adaptations to pregnancy, protecting the fetus from abnormal programming of the cardiovascular system.

The effect of dietary protein on the amino acid supply and threonine metabolism in the pregnant rat

“…In humans, the TDH pathway accounts for only 7-11% of threonine oxidation [16] in adults whereas up to 44% of oxidation is through this pathway in preterm infants [24]. Glycine is also important during gestation in rodents [25] and even a small increase in the conversion of threonine to glycine may lead to a considerable increase in the demand because of the high glycine flux. However in a preliminary experiment where animals were infused with [U-14 C] threonine on d21 of gestation, we were unable to detect any radioactivity in serum or intracellular glycine pools (Rees and Palmer unpublished results).…”

“…[25,[29][30][31]. It is becoming clear that a disturbance in maternal metabolism lies at the centre of these changes and a perturbation of amino acid metabolism may be an important mechanism.…”

Epigenetic Modification of the Renin-Angiotensin System in the Fetal Programming of Hypertension

“…11 Supplementation of low protein diets with glycine or folate reverses the programming effect of those diets. 12,13 However such a mechanism may lack gene specificity, whereas other data argues that it is specific genes that are susceptible to this effect. 14 -17 Thus in this study we set out to test the hypothesis that alteration of DNA methylation of 1 or more RAS component genes might underlie the alteration of gene expression that culminated in the development of hypertension.…”

Developmental programming of the metabolic syndrome - critical windows for intervention

“…Several maternal dietary co-factors have also been shown to prevent the development of hypertension in offspring of MLP dams although the mechanisms are not well established. Maternal supplementation with glycine [140,141] , folic acid [142,143] and choline (authors unpublished observations) has been shown to prevent programming-induced elevations in systolic blood pressure in offspring in postnatal life. There is some evidence for an epigenetic basis to these observations utilizing dietary methyl donor and co-factor supplementation; clinically relevant reductions in specific dietary inputs to the methionine/folate cycles during the periconceptional period can lead to widespread epigenetic alterations to DNA methylation in offspring and modify adult health-related phenotypes [107,115] .…”