L-Arginine effects on blood pressure and renal function of intrauterine restricted rats.
We have previously demonstrated that 3-month-old rats submitted to 50% intrauterine food restriction showed a decreased number of nephrons with increased glomerular diameter, a fact that suggests compensatory hypertrophy. In the present study, we extended the investigation and performed serial blood pressure measurements and renal function evaluation in 8- and 12-week-old rats submitted to 50% intrauterine food restriction (groups R8 and R12) and in age-matched control rats (groups C8 and C12). After weaning, six to eight animals from each group received oral supplements of 2% L-arginine ( L-arg) solution for 4 or 8 weeks (groups CA8, CA12, RA8, RA12). Our findings showed that mean blood pressure (MBP), which was significantly increased from 8 weeks on in R rats, markedly decreased after L-arg supplementation. In control animals, no alterations in MBP were observed with L-arg. Proteinuria was within normal limits in all groups studied but L-arg caused a significant decrease in this parameter in both the RA8 and RA12 groups. Glomerular filtration rate (GFR, ml/min per kg) was significantly decreased in the C8 control group (3.75+/-0.12) and in both restricted groups R8 and R12, (2.47+/-0.13 and 3.76+/-0.16, respectively) compared with the C12 group (6.09+/-0.31; P<0.05 for all comparisons). L-Arg caused an increase in GFR only in the younger groups, C8 and R8. In a separate set of experiments, acetylcholine (ACh)-induced relaxation was examined in mesenteric arteries. The R12 group showed a significant impairment of the response to ACh, which returned to normal values after L-arg supplementation. Urinary excretion of NO(x) (NO3- + NO2-) was significantly decreased in 8- and 12-week-old food-restricted rats relative to control rats. Our data indicate that, besides the known decrease in absolute nephron number, disturbances in the production/sensitivity to the L-arg-nitric oxide system may contribute to the early appearance of hypertension in the offspring of mothers submitted to significant food restriction.
Alves
Gisele Malavazi
GM
Disciplina de Fisiologia Renal e Termometabologia, Universidade Federal de São Paulo, Rua Botucatu 862, CEP 04023-900, São Paulo, Brazil.
Barão
Marco Antônio
MA
Odo
Letícia Negumi
LN
Nascimento Gomes
Guiomar
G
Franco Md
Maria do Carmo Pinho
Mdo C
Nigro
Dorothy
D
Lucas
Sandra Regina R
SR
Laurindo
Francisco Rafael Martins
FR
Brandizzi
Laura Inês Ventura
LI
Zaladek Gil
Frida
F
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D005508:Food Deprivation; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000502:physiology / Q000652:urine; D009573:Nitrites / Q000652:urine; D009929:Organ Size / Q000187:drug effects; D010927:Placental Insufficiency / Q000503:physiopathology*; D011247:Pregnancy; D011507:Proteinuria / Q000652:urine; D051381:Rats; D015430:Weight Gain / Q000187:drug effects
D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D001120:Arginine