Presented at the Neonatal Society 2004 Spring Meeting.
Passingham L1, Kurlak LO1, Gopalakrishnan GS1, Budge H1, Rhind SM2, Rae MT2, Kyle CE2, Stephenson T1, Symonds ME1
1 Centre for Reproduction and Early Life, Institute of Clinical Research, University Hospital, Nottingham, NG7 2UH, UK
2 Macaulay Institute, Craigiebuckler, Aberdeen, AB15 8QH, UK
Background : Hypertension in adult life has been linked to nutritional stress during certain fetal stages of development. Maternal nutrient restriction between 0-95 days gestation has been shown to result in an increased blood pressure in the offspring at 3 years of age (1). Both activity and mRNA expression of 11bHSD2, the enzyme which protects the mineralocorticoid receptors in the kidney, are decreased in neonatal offspring of ewes following a nutrient restricted dietary regime (30-80 days gestation) (2). The aim of this study was to explore whether this reduction persists into adulthood as a possible mechanism for the observed increase in blood pressure.
Method : A group of Scottish Blackface ewes (n=13) of similar age, weight and body composition were chosen and timed mating occurred. They were randomly assigned to a nutrient restricted (NR) group (n=6) and fed 50% of their calculated metabolised energy requirements (4 MJ/day) or a control group (n=7) and fed 100% metabolised energy requirements (8 MJ/day) up until 95 days gestation. Both groups were then fed to 100% requirements until term. The lambs were delivered naturally, weaned at 16 weeks and then grass fed until 3 years of age. The offspring were then euthanased and tissues snap frozen. The tissue enzyme activity was determined by a radiometric assay measuring conversion of tritiated cortisol to cortisone. Enzyme activities were compared between groups using a Mann-Whitney U test.
Results : 11bHSD2 enzyme activity, expressed as median and interquartile range, was significantly lower in the NR group (Mann-Whitney U, p=0.05): (C) 0.54 (0.48-0.57) pmol/min/mg protein; (NR) 0.44 (0.39-0.53) pmol/min/mg protein. Kidney weights and plasma cortisol concentrations were unaffected by previous maternal nutrient restriction (data not shown). Despite the difference in blood pressure between the groups, there was no direct correlation between enzyme activity and blood pressure.
Conclusion : Maternal nutrient restriction between early to mid-gestation results in a long term reduction in 11bHSD2 enzyme activity. The extent to which this may compromise kidney function, thereby contributing to later hypertension remains to be determined.
References
1. Gopalakrishnan GS, Gardner DS, Rhind SM, Rae MT, Kyle CE, Brooks AN, Walker RM, Ramsay MM, Keisler DH, Stephenson T, Symonds ME. Am J Physiol 2004; in press.
2. Whorwood CB, Firth KM, Budge H, Symonds ME. Endocrinology 2001;142:2854-2864.