The early gestation and postnatal environments are implicated in the development of coronary heart disease in adult life [1,2]. Previous studies have shown that undernutrition in utero leads to vascular dysfunction in fetal and adult offspring [3]. However to date it has not been determined whether these phenomenona are sex specific. In sheep we investigated the effect of moderate post-conceptional and post-weaning nutrient restriction on the vascular reactivity of the left anterior interventicular artery in male and female adult offspring. Welsh mountain sheep offspring were exposed to either 100% nutrient requirements throughout gestation and postnatal life (group CC, n=17), or to 50% nutrient requirements from conception to day 30 of gestation (term = 147 days) and a post-weaning (12-25 weeks nutrient restriction to reduced body weight to 85% of individual target weight (predicted from 0−12 week growth trajectory) and ad libitum thereafter (group UU, n=15). At 2.5 years, male (n=17) and female offspring (n=15) were killed humanely; the distal anterior interventricular artery was dissected and mounted on a wire myograph. Vascular relaxation was determined in thromboxane (10-6 M) preconstricted vessels using bradykinin (10-12-10-6 M) and adenosine (10-9-10-4 M). Data are expressed as mean ± S.E.M. and were analysed by ANOVA and a Bonferroni post-hoc test. In terms of bradykinin, there was a significant decrease in the maximal response (84.0 ± 3.3 vs 66.3 ± 5.4*, p<0.05) in UU compared to CC males. This was not seen in the females. The EC50 values of the CC and UC animals did not differ. There were no inter-group differences in the EC50 or maximal responses to adenosine in either sex. Our results suggest a sex-specific impairment of adult coronary artery dilatation in adult life by moderate early gestation and post-weaning undernutrition which could have consequences for coronary function in adult life.
University of Bristol (2005) J Physiol 567P, C4
Oral Communications: Moderate postconceptional and post-weaning undernutrition causes sex specific impairment of coronary artery function in adult sheep
Khan, Omar; Torrens, Christopher; Boullin, Julian; Tristram, Snelling; Noakes, David; Poston, Lucilla; Ohri, Sunil; Hanson, Mark; Green, Lucy;
1. DOHAD, Southampton University, Southampton, United Kingdom. 2. Wessex Cardiac Centre, Southampton, United Kingdom. 3. Maternal and Fetal Research Unit, Kings College, London, United Kingdom.
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Table 1. *P<0.05 UU significantly different from CC.
Where applicable, experiments conform with Society ethical requirements.