Barri Y M, Wilcox C S
Division of Nephrology, Hypertension and Transplantation, University of Florida College of Medicine, Gainesville, USA.
Kidney Int. 1998 May;53(5):1299-304. doi: 10.1046/j.1523-1755.1998.00857.x.
Studies in experimental animals have shown that nitric oxide (NO) generation in the kidney from L-arginine participates in adapting renal function to changes in salt intake, but similar studies in human subjects are lacking. Therefore, we compared the infusion of 30 g of L-arginine to 30 g of branched chain amino acids (control), in eight normal human subjects after 5 to 7 days of equilibration to a low salt (LS; 20 mumol.24 hr-1) or high salt (HS; 200 mumol.24 hr-1) intake. Lithium clearance was used as a marker of proximal tubular reabsorption. Compared to the control infusion, L-arginine did not significantly alter blood pressure, inulin or paraaminohippurate clearance, but significantly increased (P < 0.05) the excretion of NO2 + NO3 (NOx) (LS, 157 +/- 46 to 210 +/- 48 mumol.min-1; HS, 138 +/- 30 to 182 +/- 70) and cGMP (LS, 253 +/- 63 to 337 +/- 76 pmol.min-1; HS, 311 +/- 68 to 563 +/- 52). Renal sodium excretion was decreased by L-arginine infusion during the low salt intake (45 +/- 5 to 21 +/- 3 mumol.min-1; P < 0.05) but was increased by L-arginine during the high salt intake (298 +/- 56 to 537 +/- 84 mumol.min-1; P < 0.05). The calculated fractional reabsorption of sodium in the proximal and distal nephrons, as assessed from lithium and sodium clearances, was increased by L-arginine during the low salt intake but was decreased by L-arginine during the high salt intake. L-arginine increased plasma insulin concentration significantly (P < 0.05). This effect was independent of salt intake (LS, 67 +/- 7 to 92 +/- 13 ng.ml-1; HS, 66 +/- 7 to 76 +/- 9 ng.ml-1). L-arginine did not significantly after plasma renin activity. In conclusion, L-arginine increases the excretion of NOx and cGMP and increases plasma insulin, but the effect on sodium excretion depends upon salt intake. L-arginine enhances Na reabsorption in the proximal and distal nephrons during the low salt intake, but inhibits it during the high salt intake. Effects of L-arginine on NO and cGMP may contribute to its effects on Na reabsorption.
对实验动物的研究表明,肾脏中由L-精氨酸生成的一氧化氮(NO)参与使肾功能适应盐摄入量的变化,但缺乏对人类受试者的类似研究。因此,我们在8名正常人类受试者中,在平衡至低盐(LS;20 μmol·24小时⁻¹)或高盐(HS;200 μmol·24小时⁻¹)摄入5至7天后,比较了输注30 g L-精氨酸与输注30 g支链氨基酸(对照)的情况。锂清除率用作近端肾小管重吸收的标志物。与对照输注相比,L-精氨酸并未显著改变血压、菊粉或对氨基马尿酸盐清除率,但显著增加(P<0.05)了NO₂+NO₃(NOx)的排泄量(LS组,从157±46增至210±48 μmol·分钟⁻¹;HS组,从138±30增至182±70)以及cGMP(LS组,从253±63增至337±76 pmol·分钟⁻¹;HS组,从311±68增至563±52)。在低盐摄入期间,L-精氨酸输注使肾钠排泄减少(从45±5降至21±3 μmol·分钟⁻¹;P<0.05),但在高盐摄入期间,L-精氨酸使其增加(从298±56增至537±84 μmol·分钟⁻¹;P<0.05)。根据锂和钠清除率计算得出的近端和远端肾单位中钠的分数重吸收,在低盐摄入期间L-精氨酸使其增加,但在高盐摄入期间L-精氨酸使其减少。L-精氨酸显著增加血浆胰岛素浓度(P<0.05)。这种效应与盐摄入量无关(LS组,从67±7增至92±13 ng·毫升⁻¹;HS组,从66±7增至76±9 ng·毫升⁻¹)。L-精氨酸对血浆肾素活性没有显著影响。总之,L-精氨酸增加NOx和cGMP的排泄,并增加血浆胰岛素,但对钠排泄的影响取决于盐摄入量。在低盐摄入期间,L-精氨酸增强近端和远端肾单位中的钠重吸收,但在高盐摄入期间则抑制钠重吸收。L-精氨酸对NO和cGMP的作用可能有助于其对钠重吸收的影响。