Sahajpal Vandana, Ashton Nick
School of Biological Sciences, University of Manchester, G.38 Stopford Building, Oxford Road, Manchester M13 9PT, U.K.
Clin Sci (Lond). 2003 Jun;104(6):607-14. doi: 10.1042/CS20020355.
Recent studies have proposed a link between impaired nephrogenesis, decreased activity of the renin-angiotensin system and the onset of hypertension in rats exposed in the uterus to a maternal low-protein diet. However, there is no detailed information about renal function in this model; hence the aim of the present study was to assess renal function in young (4-week-old) rats exposed in the uterus to a maternal low-protein diet. Pregnant Wistar rats were fed isocalorific diets containing either 18% (normal protein; offspring denoted NP rats) or 9% (low protein; offspring denoted LP rats) (w/w) protein from conception until birth. At 4 weeks of age, male offspring were anaesthetized and prepared for the study of renal function, during which animals received saline alone, a bolus of enalapril (5 mg.kg(-1)) or a bolus of enalapril followed by an infusion of angiotensin II (30 ng.min(-1).kg(-1)). Under control conditions, renal haemodynamic and tubular function did not differ. However, when challenged with angiotensin II, LP rats responded with a greater decrease in glomerular filtration rate than did NP rats [NP, 2.0+/-0.2 ml.min(-1).g(-1) kidney weight ( n =9); LP, 1.0+/-0.2 ml.min(-1).g(-1) kidney weight ( n =5); P <0.05]. Renal electrolyte excretion did not differ. LP rats had significantly fewer glomeruli than NP rats ( P <0.01). Renal angiotensin II AT(1) receptor expression was increased ( P <0.01) by 24% in LP rats. It is concluded that blood pressure may be elevated in LP rats in order to maintain glomerular filtration rate against a background of fewer nephrons. Increased AT(1) receptor expression, which may arise as a result of the direct effect of protein restriction or in response to the reported decrease in renal tissue angiotensin II concentration, could also contribute to the elevated blood pressure of this model.
最近的研究表明，子宫内暴露于母体低蛋白饮食的大鼠，其肾发生受损、肾素 - 血管紧张素系统活性降低与高血压的发生之间存在联系。然而，关于该模型中肾功能的详细信息尚无报道；因此，本研究的目的是评估子宫内暴露于母体低蛋白饮食的幼年（4周龄）大鼠的肾功能。将怀孕的Wistar大鼠从受孕到分娩期间喂食含18%（正常蛋白；后代称为NP大鼠）或9%（低蛋白；后代称为LP大鼠）（w/w）蛋白质的等热量饮食。在4周龄时，对雄性后代进行麻醉并准备进行肾功能研究，在此期间动物分别接受单独的生理盐水、一剂依那普利（5 mg·kg⁻¹）或一剂依那普利后接着输注血管紧张素II（30 ng·min⁻¹·kg⁻¹）。在对照条件下，肾血流动力学和肾小管功能没有差异。然而，当用血管紧张素II刺激时，LP大鼠的肾小球滤过率下降幅度比NP大鼠更大[NP，2.0±0.2 ml·min⁻¹·g⁻¹肾重（n = 9）；LP，1.0±0.2 ml·min⁻¹·g⁻¹肾重（n = 5）；P < 0.05]。肾电解质排泄没有差异。LP大鼠的肾小球数量明显少于NP大鼠（P < 0.01）。LP大鼠肾血管紧张素II AT₁受体表达增加了24%（P < 0.01）。得出的结论是，LP大鼠的血压可能会升高，以便在肾单位较少的背景下维持肾小球滤过率。AT₁受体表达增加，这可能是蛋白质限制的直接作用结果，或者是对报道中肾组织血管紧张素II浓度降低的反应，也可能导致该模型血压升高。
