The effects of maternal protein restriction in the rat, upon programming of blood pressure, renal structure and function

Abstract

Epidemiological studies have identified an association between fetal growth impairment and adult cardiovascular disease. This has been examined experimentally using a model of maternal dietary protein restriction during pregnancy in the rat. It has been consistently demonstrated that offspring of dams supplied a low protein diet during pregnancy exhibit blood pressures elevated above those of control animals. It was proposed that hypertension in this, and other models may result from impairment of renal development, and in particular, from a relative nephron deficit. This proposal was addressed in this thesis.

Female Wistar rats were supplied either a 9% casein or an 18% casein diet during pregnancy, and parameters of offspring growth, renal structure and renal function were examined in association with blood pressure.

Exposure to a maternal dietary protein restriction either throughout pregnancy or during discrete weeks of pregnancy elevated the blood pressures of the offspring. Furthermore, it was demonstrated that offspring blood pressure was increased as a consequence of exposure to a maternal dietary protein restriction during pregnancy, regardless of the diet supplied prior to conception. Birthweight was either reduced or unaffected by prenatal exposure to a maternal low protein diet. Postnatally the kidneys were, in general, disproportionately smaller in offspring of 9% casein fed dams, compared with those of controls. Prenatal exposure to a maternal 9% casein diet resulted in offspring with 15% fewer glomeruli than control animals and impairment of nephrogenesis in late gestation. Blood pressure increased with decreasing plasma volume in 9% casein exposed offspring, but not in controls. The 9% casein exposed offspring were also shown to be resistant to the hypertensive effects of salt consumption. Examination of renal blood flow and glomerular filtration rate did not highlight any differences in renal haemodynamics between the experimental groups.

In conclusion, these data suggest that exposure to a maternal low protein diet during gestation impairs renal growth and development. This in turn may alter renal function such that blood pressure is elevated in order that body fluid homeostasis may be regulated efficiently. 

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