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

• DOI: 10.1113/jphysiol.2005.084889
• Publication Date: 2005-03-18T04:47:48Z
• Authors: Sarah J. Williams; Denise G. Hemmings; Jana M. Mitchell; I. Caroline McMillen; Sandra T. Davidge
• Keywords: Male; 0301 basic medicine; Aging; Body Weight; 3. Good health; Rats; Rats, Sprague-Dawley; 03 medical and health sciences; Pregnancy; Vascular; Prenatal Exposure Delayed Effects; Animals; Female; Endothelium; Sprague-Dawley; Endothelium, Vascular; Nitric Oxide Synthase; Food Deprivation; Hypoxia; Maternal-Fetal Exchange

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 Nω‐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.