The renin-angiotensin system (RAS) is a candidate mechanism linking altered nutrition in early life to cardiovascular dysfunction. In this study we investigated the effects of early gestation and postnatal nutrient restriction on RAS function in adulthood.
Welsh Mountain ewes received 100 % (group C, n = 37) or 50 % of global nutrient requirements (group U, n = 40) from conception to day 30 of gestation, and 100 % thereafter. Offspring were then fed either ad libitum (CC, n = 20 and UC, n = 19) or at a level that reduced body weight to 85 % of individual target weight (predicted from 0-12 wk growth trajectory) from 12 to 25 weeks postnatal age and ad libitum thereafter (CU, n = 17 and UU, n = 21). Each group contained approximately equal numbers of males and females. At ~10 months of age carotid artery loops were created under general anaesthesia (3 % halothane/O2). At ~17 months of age catheters were inserted into the carotid artery and jugular vein under general anaesthesia (3 % halothane/O2). RAS function was assessed using a frusemide challenge (5 mg kg-1 body weight; I.V.) and heart rate (HR), mean arterial blood pressure (MAP), diastolic blood pressure (DBP) and systolic blood pressure (SBP) were monitored. Data (mean ± S.E.M.) were expressed as area under the curve (AUC) and maximum response, and were analysed by ANOVA. Plasma angiotensin converting enzyme (ACE) concentrations were measured by an enzyme assay as previously described (Forhead et al. 1998) and expressed as nmol/ml/min.
We have previously shown, in males, but not females, MAP and SBP AUC were greater in CU compared to the CC group (P < 0.05) (Cleal et al. 2003). This effect of postnatal undernutrition was not seen in males exposed to early gestation nutrient restriction (UU). In males, basal plasma ACE concentrations were significantly lower (P = 0.0001) in the early gestation nutrient restricted groups (UC, 14.65 ± 0.51; UU, 13.73 ± 1.03) compared to the control groups (CC, 17.11 ± 0.51; CU, 17.98 ± 0.98). The elevated blood pressure response to frusemide in postnatal nutrient-restricted sheep was blunted by exposure to a prior early gestation nutrient restriction: this effect was associated with reduced plasma ACE concentrations.
This study suggests that the RAS is affected by a sex specific interaction between periconceptual and postnatal nutrition, which could have consequences for renal/cardiovascular function in later life.
This work was supported by the British Heart Foundation