Chronic hypoxia stimulates periarterial sympathetic nerve development in chicken embryo

Background-Epidemiological findings suggest an association between low-for- age birth weight and the risk to develop coronary heart diseases in adultho od. During pregnancy, an imbalance between fetal demands and supply may res ult in permanent alterations of neuroendocrine development in the fetus. We evaluated whether chronic prenatal hypoxia increases arterial sympathetic innervation. Methods and Results-Chicken embryos were maintained from 0.3 to 0.9 of the 21-day incubation period under normoxic (21% O-2) or hypoxic conditions (15 % O-2). At 0.9 incubation, the degree of sympathetic innervation of the emb ryonic femoral artery was determined by biochemical, histological, and func tional (in vitro contractile reactivity) techniques. Chronic hypoxia increa sed embryonic mortality (32% versus 13%), reduced body weight (21.9+/-0.4 v ersus 25.4+/-0.6 g), increased femoral artery norepinephrine (NE) content ( 78.4+/-9.4 versus 57.5+/-5.0 pg/mm vessel length), and increased the densit y of periarterial sympathetic nerve fibers (14.4+/-0.7 versus 12.5+/-0.6 co unts/10(4) mum(2)). Arteries from hypoxic embryos were less sensitive to NE (pD(2), 5.99+/-0.04 versus 6.21+/-0.10). In the presence of cocaine, howev er, differences in sensitivity were no longer present. In the embryonic hea rt, NE content (156.9+/-11.0 versus 108.1+/-14.7 pg/mg wet wt) was also inc reased after chronic hypoxia. Conclusions-In the chicken embryo, chronic moderate hypoxia leads to sympat hetic hyperinnervation of the arterial system. In humans, an analogous mech anism may increase the risk for cardiovascular disease in adult life.