Alves Gisele Malavazi, Barão Marco Antônio, Odo Letícia Negumi, Nascimento Gomes Guiomar, Franco Md Maria do Carmo Pinho, Nigro Dorothy, Lucas Sandra Regina R, Laurindo Francisco Rafael Martins, Brandizzi Laura Inês Ventura, Zaladek Gil Frida
Disciplina de Fisiologia Renal e Termometabologia, Universidade Federal de São Paulo, Rua Botucatu 862, CEP 04023-900, São Paulo, Brazil.
Pediatr Nephrol. 2002 Oct;17(10):856-62. doi: 10.1007/s00467-002-0941-z. Epub 2002 Aug 9.
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.
我们之前已经证明，对3月龄大鼠进行50%的子宫内食物限制后，其肾单位数量减少，肾小球直径增大，这一事实提示存在代偿性肥大。在本研究中，我们扩大了调查范围，对8周龄和12周龄的大鼠进行50%子宫内食物限制（R8组和R12组）以及年龄匹配的对照大鼠（C8组和C12组）进行了系列血压测量和肾功能评估。断奶后，每组6至8只动物接受2% L-精氨酸（L-arg）溶液的口服补充剂，持续4周或8周（CA8组、CA12组、RA8组、RA12组）。我们的研究结果表明，R组大鼠从8周龄起平均血压（MBP）显著升高，补充L-arg后明显降低。在对照动物中，补充L-arg未观察到MBP有变化。所有研究组的蛋白尿均在正常范围内，但L-arg使RA8组和RA12组的该参数显著降低。与C12组（6.09±0.31）相比，C8对照组（3.75±0.12）以及R8和R12两个限制组（分别为2.47±0.13和3.76±0.16）的肾小球滤过率（GFR，ml/min per kg）显著降低（所有比较P<0.05）。L-Arg仅使较年轻的C8组和R8组的GFR升高。在另一组实验中，检测了肠系膜动脉中乙酰胆碱（ACh）诱导的舒张情况。R12组对ACh的反应明显受损，补充L-arg后恢复到正常水平。相对于对照大鼠，8周龄和12周龄食物限制大鼠的尿NO(x)（NO3- + NO2-）排泄量显著降低。我们的数据表明，除了已知的绝对肾单位数量减少外，L-精氨酸-一氧化氮系统的产生/敏感性紊乱可能导致食物严重受限母亲的后代早期出现高血压。
