Effect of nutritional restriction in early pregnancy on isolated femoral artery function in mid-gestation fetal sheep

Abstract

Unbalanced maternal nutrition affects fetal endocrine and cardiovascular systems, sometimes accompanied by changes in growth, although this is usually in late gestation. We determined the effect of moderate restriction for the first half of gestation of maternal dietary protein, or of total calorific intake on isolated resistance artery function of mid-gestation fetal sheep. Welsh Mountain ewes were nutritionally restricted by 30 % of the recommended nutrient intake (globally restricted) or 30 % of the recommended protein intake (protein-restricted), compared to control ewes fed 100 % of recommended nutrient intake, for ~12 days prior to conception and for the subsequent 70 days of gestation. At mid-gestation, fetal and placental weights were similar in all dietary groups. In isolated femoral arteries, the response curve to noradrenaline was reduced in protein-restricted group fetuses (P < 0.05). Maximal relaxation (P < 0.01) and sensitivity (P < 0.05) to acetylcholine were markedly reduced in protein-restricted group fetuses, and to a smaller extent in globally restricted group fetuses (response curve, P < 0.05). The dilator response (P < 0.05) and sensitivity (P < 0.05) to the alpha2 agonist UK14304 was lower in protein-, but not in globally restricted group fetuses. The response (P < 0.05) and sensitivity (P < 0.05) to the nitric oxide donor sodium nitroprusside were reduced in protein-restricted group fetuses compared to controls. Our data show that dietary imbalance, in particular restricted protein, of the ewe can produce blunting of endothelial-dependent and -independent relaxation in systemic arteries from the mid-gestation fetus. These changes may precede perturbed late-gestation fetal and postnatal cardiovascular control.

Figure 1. Steroid profile of ewes

Maternal jugular vein plasma samples taken before conception (−13 days) and during the first half of gestation (36–45 and 52–64 days). Values are mean ± s.e.m.*P < 0.05 and **P < 0.01, significantly different from −13 days; †P < 0.01, globally restricted significantly different from control group (ANOVA and Bonferroni t test).

Figure 2. Metabolic profile of ewes

Maternal jugular vein plasma samples taken before conception (−13 days) and within two age ranges during the first half of gestation (36–45 and 52–64 days). Values are mean ± s.e.m.*P < 0.05 and **P < 0.01, significant effect of age by ANOVA and Bonferroni t test.

Figure 3. Vasorelaxation to acetylcholine (ACh), sodium nitroprusside (SNP) and UK14304 (α₂adrenoceptor agonist) in femoral arteries of fetuses from control and nutrient restricted ewes

Data are expressed as a percentage of initial preconstriction. Values are mean ± s.e.m. in control (^), 70 % global (•) and 70 % protein (▾) fetuses. *P < 0.05 (ANOVA), significantly difference from control; †P < 0.05 (ANOVA), significantly different from global group.