Chronic moderate hypoxia and protein malnutrition both induce growth retardation, but have distinct effects on arterial endothelium-dependent reactivity in the chicken embryo.

Abstract

Deviations in the rate of intrauterine growth may change organ system development, resulting in cardiovascular disease in adult life. Arterial endothelial dysfunction often plays an important role in these diseases. The effects of two interventions that reduce fetal growth, chronic hypoxia and protein malnutrition, on arterial endothelial function were investigated. Eggs of White Leghorn chickens were incubated either in room air or in 15% O2 from d 6 until d 19 of the 21-d incubation. Protein malnutrition was induced by removal of 10% of the total albumen content at d 0. In vitro reactivity of the femoral artery in response to vasodilators was measured at d 19. Both chronic hypoxia and protein malnutrition reduced embryonic body weight at d 19 by 14% without affecting relative brain weight. Chronic hypoxia or protein malnutrition did not change sensitivity to the exogenous nitric oxide donor, sodium nitroprusside (5.74 +/- 0.15 versus 5.85 +/- 0.23 and 6.05 +/- 0.18 versus 6.01 +/- 0.34, respectively). Whereas protein malnutrition did not modify arterial sensitivity to acetylcholine (7.00 +/- 0.10 versus 7.12 +/- 0.05), chronic hypoxia reduced sensitivity to this endothelium-dependent vasodilator (6.57 +/- 0.07 versus 7.02 +/- 0.06). In the presence of Nomega-nitro-l-arginine methyl ester, this difference in sensitivity to acetylcholine was no longer apparent (6.31 +/- 0.13 versus 6.27 +/- 0.06), indicating that chronic exposure to hypoxia reduced sensitivity to acetylcholine by lowering nitric oxide release. In additional experiments, a decrease in basal nitric oxide release in arteries of 3- to 4-wk-old chickens that had been exposed to in ovo chronic hypoxia was observed (increase in K+ contraction: -0.16 +/- 0.33 N/m versus 0.68 +/- 020 N/m). Protein malnutrition and chronic hypoxia both induce disproportionate growth retardation, but only the latter impairs arterial endothelial function. Intrauterine exposure to chronic hypoxia induces changes in arterial endothelial properties that may play a role in the development of cardiovascular disease in adult life.