Effects of undernutrition in early pregnancy on systemic small artery function in late-gestation fetal sheep

OBJECTIVE: The aim of this study was to investigate functional development of small arteries from the skeletal circulation of fetal sheep and to deter mine whether maternal undernutrition affects responses to vasoconstrictive and vasodilatory agonists in arteries from the late-gestation fetus. STUDY DESIGN: We investigated vasoconstrictive and vasodilatory responses o f isolated small (approximately 300 mum) arteries from the femoral vascular bed of fetal sheep and from late-gestation pregnant ewes. Ewes were fed ei ther 100% of the nutritional requirement throughout pregnancy (control grou p) or a restricted diet of 85% or 50% of the nutritional requirement for th e first 70 days of pregnancy. For the remainder of pregnancy all ewes were fed the complete diet. RESULTS: Among control group animals vasoconstriction in response to norepi nephrine was well developed in fetuses at 0.6 and 0.9 gestation with respec t to that in the ewes. When expressed as a percentage of the response to 12 5-mmol/L potassium (to correct for differences in vessel size and muscle ma ss), maximum constriction in response to norepinephrine was greater in feta l vessels from 0.9 gestation than in either those at 0.6 gestation or those of the ewes. Endothelium-dependent vasorelaxation responses to acetylcholi ne and bradykinin were also well developed in fetuses at 0.6 and 0.9 gestat ion and were similar to those in the ewes, In fetuses at 0.9 gestation the 50% nutritional restriction of the ewe led to blunted endothelium-dependent vasodilatation in response to acetylcholine and blunted endothelium-indepe ndent vasodilatation in response to sodium nitroprusside. Responses in the fetuses at 0.9 gestation in which the ewes were fed a restricted diet of 85 % were normal. CONCLUSION: This study shows that from midgestation onward small arteries f rom the skeletal circulation of the fetal sheep have the functional capacit y to respond to norepinephrine and endothelium-dependent vasodilators leg, acetylcholine and bradykinin). The blunted responses to acetylcholine and s odium nitroprusside in the fetuses at 0.9 gestation among the group of diet arily restricted ewes (restricted diet of 50% group) were indicative of imp aired vascular smooth muscle sensitivity to nitric oxide. This defect may c ontribute to the development of hypertension in later life.