The selfish brain and the Barker hypothesis

1. Brain sparing is a feature of intra-uterine growth retardation (IUGR). This implies that there is a redistribution of metabolic supply so that body growth slows to a greater extent than brain growth. 2. Intra-uterine growth retardation, as evidenced by a low birthweight for gestational age is a predisposing factor for hypertension, cardiovascular disease and diabetes mellitus in adult life. 3. In species like humans, nephrogenesis is complete before birth. In the rat, it is completed shortly after birth. In both species, it can be shown that either undernutrition or IUGR is associated with reduced nephron number. 4. It has been proposed that oligonephropathy results in hyperfiltration, which ultimately leads to glomerulosclerosis and hypertension. The renin-angiotensin system (RAS) is necessary for normal renal development and fetal renal function. In the rat, blockade of the RAS in the first weeks of life by pharmacological agents reduces glomerular number and has been shown to cause hypertension in adult life. Renal denervation reduces the activity of the fetal RAS and also causes abnormal development of the renin-secreting cells. 5. There is tonic renal sympathetic nerve activity in the late gestation fetal sheep. The level of renal sympathetic nerve activity (RSNA) is influenced by the fetal behavioural state. 6. However, interactions between the developing kidney and the developing sympathetic nervous system are poorly understood. On the one hand, renal innervation may be important in the provision of neurotrophic factors that stimulate the development of the RAS and kidney. On the other, high levels of RSNA associated with circulating catecholamines and vasopressin may cause vasoconstriction and limit nephrogenesis. This latter effect could be a predisposing factor to adult hypertension and cardiovascular disease.