McKillop I, Haylor J, el Nahas A M
Sheffield Kidney Institute, Northern General Hospital, UK.
Exp Nephrol. 1995 Jan-Feb;3(1):49-57.
IGF-I is known to increase renal function when administered in vivo. To establish whether IGF-I has a direct effect on renal function, the present experiments were performed to measure the effects of IGF-I in the isolated perfused rat kidney (IPRK). We have examined the influence of l-nitroarginine methyl ester (l-NAME), a non-selective inhibitor of nitric oxide synthase (NOS) and aminoguanidine (AG), a selective inhibitor of the inducible isoform of NOS on the direct effects of recombinant human IGF-I (rhIGF-I) on renal function in the IPRK. rhIGF-I (100 nM) increased both glomerular filtration rate (GFR) (+109 +/- 17%, n = 6, p < 0.01) and renal perfusate flow (RPF) (+100 +/- 15%, n = 6, p < 0.01), effects which were completely blocked by l-NAME (10 microM). In the presence of the enantiomer d-NAME (10 microM, n = 6) which is not an inhibitor of NOS, rhIGF-I (100 nM) still produced a significant increase in both GFR (+175 +/- 15%, n = 6, p < 0.01) and RPF (+94 +/- 7%, n = 6, p < 0.01). AG blunted the renal haemodynamic response to rhIGF-I (GFR +49 +/- 10, RPF + 31 +/- 7, n = 6, p < 0.05), but unlike l-NAME, did not abolish it. The haemodynamic responses of the IPRK to rhIGF-I in the presence of AG were significantly greater than those of rhIGF-I in the presence of l-NAME (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
已知胰岛素样生长因子-I（IGF-I）在体内给药时可增强肾功能。为确定IGF-I是否对肾功能有直接作用，进行了本实验以测量IGF-I对离体灌注大鼠肾脏（IPRK）的影响。我们研究了一氧化氮合酶（NOS）的非选择性抑制剂L-硝基精氨酸甲酯（L-NAME）和诱导型NOS同工型的选择性抑制剂氨基胍（AG）对重组人IGF-I（rhIGF-I）对IPRK肾功能直接作用的影响。rhIGF-I（100 nM）可使肾小球滤过率（GFR）升高（+109±17%，n = 6，p < 0.01）和肾灌注液流量（RPF）升高（+100±15%，n = 6，p < 0.01），这些作用被L-NAME（10 μM）完全阻断。在不是NOS抑制剂的对映体D-NAME（10 μM，n = 6）存在的情况下，rhIGF-I（100 nM）仍使GFR（+175±15%，n = 6，p < 0.01）和RPF（+94±7%，n = 6，p < 0.01）显著升高。AG减弱了对rhIGF-I的肾血流动力学反应（GFR +49±10，RPF + 31±7，n = 6，p < 0.05），但与L-NAME不同，并未消除该反应。在AG存在的情况下，IPRK对rhIGF-I的血流动力学反应显著大于在L-NAME存在时rhIGF-I的反应（p < 0.05）。（摘要截短于250字）
