Sex-Specific Effects of Prenatal Low-Protein and Carbenoxolone Exposure on Renal Angiotensin Receptor Expression in Rats

Abstract

Experimental models have shown the developing cardiovascular and renal systems to be sensitive to mild shifts in maternal nutrition, leading to altered function and risk of disease in adult life. The offspring of Wistar rats fed a low-protein diet during pregnancy exhibit a reduced nephron number and hypertension in postnatal life, providing a useful tool to examine the mechanistic basis of programming. Evidence indicates that upregulation of the renin-angiotensin system plays an important role, in particular through receptor-mediated changes in angiotensin II activity. However, although programmed hypertension has proven dependent on maternal glucocorticoids, there appear to be conflicting effects of prenatal low-protein and glucocorticoid exposure on postnatal angiotensin receptor expression. This study aimed to resolve this issue by comparing the effects of low-protein and glucocorticoid exposures on postnatal nephron number and angiotensin receptor expression. In addition, this study examined the modulation of prenatal treatment effects by postnatal inhibition of type 1 angiotensin receptor. The data demonstrates that whereas prenatal low-protein and glucocorticoid exposure have a similar effect in reducing nephron number, there are age- and gender-related differences in their effects on postnatal angiotensin receptor expression. In addition, this study provides novel evidence of a substantial upregulation of type 2 angiotensin receptor expression in low-protein- and glucocorticoid-exposed female offspring at 20 weeks of age, with implications for subsequent renal remodeling and function. Despite being targeted to the postnephrogenic period, inhibition of type 1 angiotensin receptor had an inhibitory effect on renal and somatic growth, additionally indicating its unsuitability during early life.