Effects of Intrauterine Food Restriction and Long-Term Dietary Supplementation with l-Arginine on Age-Related Changes in Renal Function and Structure of Rats

Abstract

We have previously demonstrated that restricting intrauterine food by 50% in 3-mo-old rats produced lower nephron numbers and early-onset hypertension, the latter being normalized by l-arginine administration. In 18-mo-old rats, such restriction increased glomerulosclerosis. In this study, we expanded our investigation, evaluating functional, morphologic, and immunohistochemical parameters in intrauterine-food-restricted 18-mo-old rats, either receiving l-arginine (RA18) or not (R18). Age-matched, non-food-restricted controls were assigned to similar groups with l-arginine (CA18) and without (C18). After weaning, l-arginine was given daily for 17 mo. No functional or morphologic changes were observed in C18 rats. The R18 rats developed early-onset hypertension, which persisted throughout the observation period, as well as significant proteinuria from 12 mo on. In RA18 rats, l-arginine decreased both blood pressure levels and proteinuria, and glomerular diameter was significantly smaller than in R18 rats (115.63 ± 2.2versus134.8 ± 1.0 μgm, p “ 0.05). However, in RA18 rats, glomerular filtration rate remained depressed. Although l-arginine prevented glomerulosclerosis (R18 = 14%, RA18 = 4%;p“ 0.05), glomerular expression of fibronectin and desmin was still greater in RA18 rats than in controls. Our data show that, although l-arginine prevented hypertension and proteinuria, glomerular injury still occurred, suggesting that intrauterine food restriction may be one of the leading causes of impaired renal function in adult life. Abbreviations GFR glomerular filtration rate l-Argl-arginine NOSnitric oxide synthase PAHpara-aminohippurate RPFrenal plasma flow SHRspontaneously hypertensive rat. © International Pediatrics Research Foundation, Inc. 2005. All Rights Reserved.