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Type: Journal article
Title: Effects of maternal hypoxia or nutrient restriction during pregnancy on endothelial function in adult male rat offspring
Author: Williams, S.
Hemmings, D.
Mitchell, J.
McMillen, I.
Davidge, S.
Citation: Journal of Physiology-London, 2005; 565(1):125-135
Publisher: Blackwell Publishing Ltd
Issue Date: 2005
ISSN: 0022-3751
Statement of
Sarah J. Williams, Denise G. Hemmings, Jana M. Mitchell, I. Caroline McMillen and Sandra T. Davidge
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.
Keywords: Endothelium, Vascular; Animals; Rats; Rats, Sprague-Dawley; Prenatal Exposure Delayed Effects; Body Weight; Food Deprivation; Aging; Pregnancy; Maternal-Fetal Exchange; Female; Male; Nitric Oxide Synthase; Hypoxia
RMID: 0020050497
DOI: 10.1113/jphysiol.2005.084889
Appears in Collections:Molecular and Biomedical Science publications

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