Bosse H M, Böhm R, Resch S, Bachmann S
Department of Anatomy and Cell Biology I, University of Heidelberg, Germany.
Am J Physiol. 1995 Dec;269(6 Pt 2):F793-805. doi: 10.1152/ajprenal.1995.269.6.F793.
Four chronic experiments were performed to assess changes in the activity and gene expression of type I nitric oxide synthase (NOS) at the macula densa (MD) and of renin expression and immunoreactivity (IR) at the juxtaglomerular apparatus (JGA) of rat kidney, as follows: 1) two-kidney, one-clip Goldblatt hypertension (2K1C, for 3 and 40 days; sham operation for controls), 2) furosemide treatment (150 mg/kg-1.day-1 ip for 5 days), 3) chronic low-salt diet (0.02%) vs. high-salt diet (3%; both for 11 days), and 4) chronic blockade of NOS by nitro-L-arginine methyl ester (L-NAME, 40 mg.kg-1.day-1 for 2 mo). NOS and renin gene expression, NOS enzyme activity and renin IR were semiquantitatively evaluated with histochemical methods (NADPH diaphorase, in situ hybridization, immunohistochemistry). In 2K1C, marked increases were induced in NOS and renin in the ischemic vs. contralateral kidneys both after 3 and 40 days, respectively (P < 0.05). Related to controls, significant increases in the ischemic kidney were encountered after 3 and 40 days, whereas contralateral suppression of NOS and renin was found only after 40 days. Furosemide treatment resulted in a marked increase of both NOS and renin levels compared with controls (P < 0.05). Salt restriction induced a significant elevation of NOS levels compared with salt loading (P < 0.05), whereas only minor changes were evident in renin levels. L-NAME treatment resulted in a moderate reduction of NOS activity (not significant), whereas renin levels were markedly reduced (P < 0.05). These results show that NOS activity and gene expression are inversely related to chronic changes in renal perfusion, salt balance, and salt transport at the distal tubule in parallel with the known response of renin to these changes. Inhibition of NOS decreases renin levels at the JGA. The histochemical findings support previous concepts that MD-derived NO is involved in the control of renin synthesis.
进行了四项慢性实验，以评估大鼠肾脏致密斑（MD）处 I 型一氧化氮合酶（NOS）的活性和基因表达以及肾小球旁器（JGA）处肾素表达和免疫反应性（IR）的变化，具体如下：1）两肾一夹 Goldblatt 高血压模型（2K1C，分别持续 3 天和 40 天；假手术作为对照），2）速尿治疗（150mg/kg-1·天-1 腹腔注射，持续 5 天），3）慢性低钠饮食（0.02%）与高钠饮食（3%；均持续 11 天），4）用硝基-L-精氨酸甲酯（L-NAME，40mg·kg-1·天-1，持续 2 个月）慢性阻断 NOS。采用组织化学方法（NADPH 黄递酶、原位杂交、免疫组织化学）对 NOS 和肾素基因表达、NOS 酶活性和肾素 IR 进行半定量评估。在 2K1C 模型中，分别在 3 天和 40 天后，缺血肾与对侧肾相比，NOS 和肾素均显著增加（P<0.05）。与对照组相比，3 天和 40 天后缺血肾出现显著增加，而仅在 40 天后对侧肾的 NOS 和肾素受到抑制。速尿治疗导致与对照组相比，NOS 和肾素水平均显著增加（P<0.05）。与高盐负荷相比，限盐导致 NOS 水平显著升高（P<0.05），而肾素水平仅出现轻微变化。L-NAME 治疗导致 NOS 活性适度降低（无显著性差异），而肾素水平显著降低（P<0.05）。这些结果表明，NOS 活性和基因表达与肾脏灌注、盐平衡和远端小管盐转运的慢性变化呈负相关，这与肾素对这些变化的已知反应一致。抑制 NOS 可降低 JGA 处的肾素水平。组织化学结果支持了先前的概念，即致密斑来源的 NO 参与肾素合成的调控。
