Fernández-Repollet E, Tapia E, Martínez-Maldonado M
Department of Pharmacology, University of Puerto Rico, School of Medicine, San Juan.
J Clin Invest. 1987 Oct;80(4):1045-9. doi: 10.1172/JCI113158.
We assessed the role of angiotensin II in mediating the alterations in renal hemodynamics known to result from low protein feeding to normal rats by examining the effect of the angiotensin-converting enzyme (ACE) inhibitor captopril. 2 wk of low protein (6% casein) diet resulted in decreased glomerular filtration rate (normal protein [NP], 1.82 +/- 0.17 vs. low protein [LP], 0.76 +/- 0.01 ml/min; P less than 0.05) and renal plasma flow (NP, 6.7 +/- 0.2 vs. LP, 3.3 +/- 0.3 ml/min; P less than 0.05); renal vascular resistance rose (NP, 8.7 +/- 0.4 vs. LP, 19.8 +/- 1.4 dyn . s per cm5; P less than 0.05). These changes were accompanied by a significant decrease in plasma renin activity (NP, 7.0 +/- 0.7 vs. LP, 4.4 +/- 0.8 ng A I/ml per h; P less than 0.05), plasma aldosterone concentration (NP, 7.0 +/- 0.6 vs. LP, 4.1 +/- 0.7 ng/dl; P less than 0.05), and urinary PGE2 excretion (NP, 3,120 +/- 511 vs. LP, 648 +/- 95 pg/mgCr; P less than 0.05); by contrast renal renin content was significantly increased (NP, 2,587 +/- 273 vs. LP, 7,032 +/- 654 ng A I/mg protein; P less than 0.05). Treatment with captopril (30 mg/kg per d) raised glomerular filtration rate (GFR; LP + capt, 1.6 +/- 0.2 ml/min) and renal plasma flow (RPF; LP + capt, 6.7 +/- 0.7 ml/min), and reduced renal vascular resistance (LP + capt, 9.2 +/- 0.5 dyn/s per cm5) in low protein-fed animals. These values were not different from those measured in untreated and captopril-treated rats fed a normal (23%) protein diet. There were no changes in systemic mean arterial pressure in any group of rats. These data provide evidence that intrarenal angiotensin II mediates the changes in intrarenal hemodynamics induced by protein deprivation. The effects of low protein feeding may be partly potentiated by the reduction in PGE2 synthesis. However, the normalization of GFR and RPF in view of only modest increases in PGE2 excretion after captopril (LP, 648 +/- 95 vs. LP + capt, 1,131 +/- 82 pg/mgCr; P less than 0.05) suggests that if PGE2 is involved in these changes, it plays a permissive but not essential role in the increased renovascular resistance.
我们通过检测血管紧张素转换酶（ACE）抑制剂卡托普利的作用，评估了血管紧张素II在介导正常大鼠低蛋白喂养所致肾血流动力学改变中的作用。低蛋白（6%酪蛋白）饮食2周导致肾小球滤过率降低（正常蛋白[NP]组为1.82±0.17 vs.低蛋白[LP]组为0.76±0.01 ml/min；P<0.05）以及肾血浆流量降低（NP组为6.7±0.2 vs. LP组为3.3±0.3 ml/min；P<0.05）；肾血管阻力升高（NP组为8.7±0.4 vs. LP组为19.8±1.4 dyn·s/cm5；P<0.05）。这些变化伴随着血浆肾素活性显著降低（NP组为7.0±0.7 vs. LP组为4.4±0.8 ng AI/ml per h；P<0.05）、血浆醛固酮浓度降低（NP组为7.0±0.6 vs. LP组为4.1±0.7 ng/dl；P<0.05）以及尿PGE2排泄减少（NP组为3,120±511 vs. LP组为648±95 pg/mgCr；P<0.05）；相比之下，肾肾素含量显著增加（NP组为2,587±273 vs. LP组为7,032±654 ng AI/mg蛋白；P<0.05）。用卡托普利（30 mg/kg per d）治疗可提高低蛋白喂养动物的肾小球滤过率（GFR；LP+卡托普利组为1.6±0.2 ml/min）和肾血浆流量（RPF；LP+卡托普利组为6.7±0.7 ml/min），并降低肾血管阻力（LP+卡托普利组为9.2±0.5 dyn/s per cm5）。这些值与未治疗和用卡托普利治疗的正常（23%）蛋白饮食大鼠所测值无差异。任何一组大鼠的全身平均动脉压均无变化。这些数据证明肾内血管紧张素II介导了蛋白质缺乏引起的肾内血流动力学变化。低蛋白喂养的作用可能部分因PGE2合成减少而增强。然而，鉴于卡托普利治疗后PGE2排泄仅适度增加（LP组为648±95 vs. LP+卡托普利组为1,131±82 pg/mgCr；P<0.05），GFR和RPF恢复正常表明，如果PGE2参与这些变化，它在肾血管阻力增加中起允许作用但非必需作用。
