Effects of maternal hypoxia or nutrient restriction during pregnancy on endothelial function in adult male rat offspring

Compromised fetal growth impairs vascular function; however, it is unclear whether chronic hypoxia in utero affects adult endothelial function. We hypothesized that maternal hypoxia (H, 12% O₂, n = 9) or nutrient restriction (NR, 40% of control, n = 7) imposed from day 15–21 pregnancy in rats would impair endothelial function in adult male offspring (relative to control, C, n = 10). Using a wire myograph, endothelium-dependent relaxation in response to methacholine was assessed in small mesenteric arteries from 4- and 7-month-old (mo) male offspring. Nitric oxide (NO) mediation of endothelium-dependent relaxation was evaluated using N ^ω-nitro- l -arginine methyl ester ( l -NAME; NO synthase inhibitor). Observed differences in the NO pathway at 7 months were investigated using exogenous superoxide dismutase (SOD) to reduce NO scavenging, and sodium nitroprusside (SNP; NO donor) to assess smooth muscle sensitivity to NO. Sensitivity to methacholine-induced endothelium-dependent relaxation was reduced in H offspring at 4 months ( P < 0.05), but was not different among groups at 7 months. l -NAME reduced methacholine sensitivity in C ( P < 0.01), H ( P < 0.01) and NR ( P < 0.05) offspring at 4 months, but at 7 months l -NAME reduced sensitivity in C ( P < 0.05), tended to in NR ( P = 0.055) but had no effect in H offspring. SOD did not alter sensitivity to methacholine in C, but increased sensitivity in H offspring ( P < 0.01). SNP responses did not differ among groups. In summary, prenatal hypoxia, but not nutrient restriction impaired endothelium-dependent relaxation at 4 months, and reduced NO mediation of endothelial function at 7 months, in part through reduced NO bio-availability. Distinct effects following reduced maternal oxygen versus nutrition suggest that decreased oxygen supply during fetal life may specifically impact adult vascular function.