Modulation of ANG II receptor and its mRNA in normal rat by low-protein feeding.
Modulation of ANG II receptor and its mRNA in normal rat by low-protein feeding.
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DOI：
10.1152/ajprenal.1993.265.5.f660
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
J. Benabe;S. Wang;J. Wilcox;M. Martínez‐Maldonado
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文献类型：
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作者：
J. Benabe;S. Wang;J. Wilcox;M. Martínez‐Maldonado
低蛋白喂养导致正常、完整大鼠血浆肾素活性（PRA）降低、前列腺素生成降低、肾内血管阻力升高、肾血浆流量（RPF）和肾小球滤过率（GFR）降低。转换酶抑制剂可逆转血流动力学变化。在本研究中，正常大鼠分别饲喂正常蛋白（NP）和低蛋白（LP）。NP的PRA为10.1 +/- 1.3 ng，而NP为5.1 +/- 1.7 ng。LP为ml-1 × h-1 （P < 0.001）。在使用氯沙坦（DuP-753，一种特异性血管紧张素at1受体抑制剂）治疗期间，LP和NP大鼠的平均动脉压均下降，但LP +氯沙坦组的GFR和RPF与NP和NP +氯沙坦组的值没有区别。血浆钠、钾和尿液中这两种电解质的排泄量没有变化。血管紧张素II （ANG II）与离体肾小球（n = 19）的分离常数分别为1.11 +/- 0.22和1.22 +/- 0.20 nM（无统计学意义），最大结合蛋白为763 +/- 89和432 +/- 75 fmol/mg (P < 0.001)，表明受体数量增加，但LP的亲和力没有变化。定量放射自显影也观察到LP与NP相比受体数量增加。这些结果反映了LP对ANG II反应的主要肾内改变。Northern blot和原位杂交分析显示，AT1受体mRNA在LP的皮质（肾小球）和髓质中表达增强。膳食蛋白质是ANG II在肾内作用的重要调节剂。我们首次发现饮食中的蛋白质调节AT1受体基因的表达，ANG II通过AT1受体介导LP摄食的血流动力学变化。
Low-protein feeding results in reduced plasma renin activity (PRA), low prostaglandin production, high intrarenal vascular resistance, and reduced renal plasma flow (RPF) and glomerular filtration rate (GFR) in normal, intact rats. The hemodynamic changes are reversed by converting enzyme inhibitors. In this study, normal rats were fed normal protein (NP) or low protein (LP). PRA was 10.1 +/- 1.3 for NP vs. 5.1 +/- 1.7 ng.ml-1 x h-1 for LP (P < 0.001). Mean arterial pressure fell in both LP and NP during treatment with losartan (DuP-753, a specific angiotensin AT1-receptor inhibitor), but GFR and RPF in LP + losartan became indistinguishable from values obtained in NP and NP + losartan rats. Plasma Na and K and urine excretions of these two electrolytes were unchanged. Angiotensin II (ANG II) binding to isolated glomeruli (n = 19) revealed a dissociation constant of 1.11 +/- 0.22 vs. 1.22 +/- 0.20 nM (not significant) and maximal binding of 763 +/- 89 vs. 432 +/- 75 fmol/mg protein (P < 0.001), indicating an increased number of receptors without changes in affinity in LP. An increased number of receptors in LP compared with NP was also observed by quantitative autoradiography. These results reflect a predominant intrarenal alteration in the response to ANG II in LP. Northern blot and in situ hybridization analysis of the AT1 receptor mRNA showed enhanced gene expression in cortex (glomeruli) and medulla in LP. Dietary protein is an important modulator of the intrarenal actions of ANG II. We show for the first time that protein in the diet modulates the expression of the AT1 receptor gene and that ANG II mediates the hemodynamic changes of LP feeding through the AT1 receptor.