title: 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 +/- 2.2 versus 134.8 +/- 1.0 mum, 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.
authors.affiliation: Department of Physiology, Renal Physiology, and Metabolic Biology, UNIFESP-EPM, São Paulo, Brazil, 04023-900. frida@ecb.epm.br
authors.forename: Frida Zaladek
authors.initials: FZ
authors.lastname: Gil
authors.forename: Sandra Regina R
authors.initials: SR
authors.lastname: Lucas
authors.forename: Guiomar Nascimento
authors.initials: GN
authors.lastname: Gomes
authors.forename: Maria De Fátima
authors.initials: Mde F
authors.lastname: Cavanal
authors.forename: Terezila Machado
authors.initials: TM
authors.lastname: Coimbra
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000375:Aging; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001794:Blood Pressure; D019587:Dietary Supplements; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology; D005353:Fibronectins / Q000378:metabolism; D005508:Food Deprivation; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000209:etiology; D007150:Immunohistochemistry; D007668:Kidney / Q000196:embryology* / Q000378:metabolism* / Q000473:pathology; D010927:Placental Insufficiency / Q000503:physiopathology*; D011247:Pregnancy; D011270:Pregnancy, Animal; D011297:Prenatal Exposure Delayed Effects; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000199:Actins; D005353:Fibronectins; D001120:Arginine