Effects of intrauterine food restriction and long-term dietary supplementation with L-arginine on age-related changes in renal function and structure of rats.
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.
Gil
Frida Zaladek
FZ
Department of Physiology, Renal Physiology, and Metabolic Biology, UNIFESP-EPM, São Paulo, Brazil, 04023-900. frida@ecb.epm.br
Lucas
Sandra Regina R
SR
Gomes
Guiomar Nascimento
GN
Cavanal
Maria De Fátima
Mde F
Coimbra
Terezila Machado
TM
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
D000199:Actins; D005353:Fibronectins; D001120:Arginine