APPS November 2002 Meeting Abstract 302

Eugenie R. Lumbers, Department of Physiology & Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW.

The kidney, through control of salt and water homeostasis and via the renin angiotensin system (RAS) plays a pivotal role in the development of many forms of hypertension in the adult. Thus it is not surprising that investigations into programming for hypertension in adult life have examined the effects of undernutrition on the developing kidney and RAS.

Abnormal renal development occurs in growth retarded human fetuses. Abnormalities in renal development also occur in animals when components of the developing RAS are blocked pharmacologically or `knocked-out' ^1,2. In fetal sheep chronic undernutrition and hypoxaemia due to long term placental insufficiency were associated with reduced expression of the renal renin gene and reduced renal renin levels³. However in normoxic fetal sheep subjected to chronic hypoglycaemia, renal renin gene expression and renal renin levels were no different from control values. Since there was a positive correlation between fetal arterial PO₂ and fetal renal renin mRNA in placentally insufficient fetal sheep, it is possible that the reduced expression of renal renin is related to chronic hypoxaemia rather than undernutrition.

In the rat however, renal renin levels and impairment of renal development are strongly related to maternal undernutrition. Maternal protein restriction results in offspring that have reduced renal renin levels, reduced glomerular number and hypertension ⁴.

In the fetal sheep, activity of both the circulating and renal RASs is strongly stimulated by IGF-I⁵ which in turn is regulated by the level of fetal nutrition. High levels of fetal IGF-I are associated with increased renal mass and left ventricular hypertrophy but there is no effect on fetal arterial pressure. On the other hand, IGF-I had no effect on the low plasma renin levels of adult rats subjected to prenatal undernutrition.

(2) Esther CR, Marino EM, Howard TE, Machaud A, Corvol P, Capecchi, MR, Bernstein KE. Journal of Clinical Investigation. 1997;99:2375-2385.