Parallel regulation of constitutive NO synthase and renin at JGA of rat kidney under various stimuli
Parallel regulation of constitutive NO synthase and renin at JGA of rat kidney under various stimuli
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DOI：
10.1152/ajprenal.1995.269.6.f793
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发表时间：
1995-12-01
影响因子：
4.2
通讯作者：
Bachmann, S
中科院分区：
文献类型：
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作者：
Bosse, HM;Bohm, R;Bachmann, S
进行了四项长期实验来评估大鼠致密斑（MD）处I型一氧化氮合酶（NOS）活性和基因表达的变化以及大鼠肾近肾小球装置（JGA）处肾素表达和免疫反应性（IR）的变化，具体如下：1）两肾单夹Goldblatt高血压（2K1C，持续3天和40天，对照为假手术），2）速尿治疗（150 mg . kg(-1). day(-1) ip，持续 5 天），3) 长期低盐饮食 (0.02%) 与高盐饮食（3%；均持续 11 天），以及 4) 硝基-L-精氨酸甲酯（L-NAME，40 mg . kg(-1). day(-1)，持续 2 个月）慢性阻断 NOS。采用组织化学方法（NADPH 心肌酶、原位杂交、免疫组织化学）半定量评估 NOS 和肾素基因表达、NOS 酶活性和肾素 IR。在 2K1C 中，3 天和 40 天后，缺血肾脏中的 NOS 和肾素分别与对侧肾脏相比显着增加（P < 0.05）。与对照相比，3天和40天后肾脏缺血显着增加，而仅在40天后才发现对侧NOS和肾素抑制。与对照组相比，呋塞米治疗导致 NOS 和肾素水平显着升高（P < 0.05）。与盐负荷相比，限盐导致 NOS 水平显着升高（P < 0.05），而肾素水平仅出现微小变化。 L-NAME 治疗导致 NOS 活性中度降低（不显着），而肾素水平显着降低（P < 0.05）。这些结果表明，NOS 活性和基因表达与肾灌注、盐平衡和远端肾小管盐转运的慢性变化呈负相关，与肾素对这些变化的已知反应平行。 NOS 的抑制会降低 JGA 的肾素水平。组织化学结果支持了先前的观点，即 MD 衍生的 NO 参与肾素合成的控制。
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.