title: Effects of maternal hypoxia or nutrient restriction during pregnancy on endothelial function in adult male rat offspring.
abstract: 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(omega)-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.
authors.affiliation: Perinatal Research Centre, Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Canada T6G 2S2.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Williams
authors.forename: Denise G
authors.initials: DG
authors.lastname: Hemmings
authors.forename: Jana M
authors.initials: JM
authors.lastname: Mitchell
authors.forename: I Caroline
authors.initials: IC
authors.lastname: McMillen
authors.forename: Sandra T
authors.initials: ST
authors.lastname: Davidge
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005508:Food Deprivation; D000860:Hypoxia / Q000196:embryology / Q000503:physiopathology*; D008297:Male; D008431:Maternal-Fetal Exchange; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019001:Nitric Oxide Synthase