Mechanisms regulating glomerular hemodynamics

肾小球血流动力学的调节机制

• 批准号: 12470208
• 负责人: ITO Sadayoshi
• 金额: $ 8.96万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470208/
• 关键词: ZO-HETE; EET; macula densa; tubuloglomenular feedback; nitric oxide; microperfusion; juxtaglomenular apparatus; adenosine; 輸入細動脈; 緻密斑; アラキドン酸代謝物; チトクロームP450; P450 4A; ブラジキニン; nitric oxide; アンジオテンシン変換酵素阻害薬

Renal hemodynamics play an important role in the pathophysiology of hypertension and progressive renal dysfunction. The juxtaglomerular apparatus, composed of glomerular afferent and efferent arterioles and the macula densa, regulates the glomerular hemodynamics. It has recently been shown that nitric oxide (NO), adenosine (Ado) and the cytochrome P450 metabolites of arachidonic acid (20-HETE and EET) plays an important modulatory role in the JGA function. In this study, in order to examine the function of the JGA directly, we employed preparations of isolated microperfused afferent arterioles with or without attached macula densa perfused. Result are as follow.1)When the NaCl concentration of the macula densa perfusate was increased, the afferent arteriole exhibited constriction, the phenomenon called TGF, this response was abolished by pretreatment with Ado Al receptor. On the other hand, administration of a low dose of Ado into the afferent ceteriolar but not macula densa perfusate … More augmented the TGF-induced constriction. These results suggest that Ado and its Al receptor are essential to the signal augmented the TGF-induced constriction. These results suggest that Ado and its Al receptor are essential to the signal transmission of TGF, and the site of action seems to be the JGA interstitium/vascularture but not the tubular lumen.2)When reuronal nitric oxide synthase (nNOS) in the macula densa was inhibited acutely, afferent arteriolar constriction-induced by TGF was augmented, while in nNOS knockout mice, TGF remained unaltered, possibly due to some unknown adaptation mechanisms. In addition, results suggest that during a low sodium intake, the macula densa NO production is enhanced, thereby opposing the vasoconstrictor action of angiotensin ll (All) and maintaining renal blood flow.3)The All-induced vasoconstriction of microperfused afferent arterioles was augmented by blockade of EET synthesis. This effect was abolished by blocking AT2 receptors, suggesting that All stimulates synthesis of the vasodilator EET via AT2 receptors.4)ACE inhibitors induced cytochrome P450 enzyme expression and thereby enhance synthesis of 20-HETE and EET in microsome fractions of the kidney. This enhancement seems to be mediated by ACE inhibitor-induced elevation of tissue kinin levels. Thus, the present study clarifies, in part, the role of NO,Ado,20-HETE and EE in the regulation of TGA function. Less

肾血流动力学在高血压和进行性肾功能不全的病理生理过程中起重要作用。肾小球器由肾小球的输入和输出小动脉以及致密斑组成，调节肾小球的血流动力学。最近的研究表明，一氧化氮（NO），腺苷（Ado）和花生四烯酸的细胞色素P450代谢产物（20-HETE和EET）在JGA功能中起着重要的调节作用。在这项研究中，为了直接检查JGA的功能，我们采用了离体微灌注的传入小动脉与或不附着致密斑灌注的制剂。结果如下：1）当致密斑灌流液中NaCl浓度增加时，传入小动脉出现收缩，即TGF-β效应，Ado-Al受体预处理可消除这种效应。另一方面，低剂量的Ado注入传入小脑而不是致密斑灌注液， ...更多信息 增强TGF诱导的收缩。这些结果表明，Ado及其Al受体在信号增强TGF诱导的收缩中是必需的。这些结果提示Ado及其Al受体在TGF信号传递中起重要作用，其作用部位可能是JGA血管壁/血管结构，而不是肾小管腔。2）当致密斑神经元型一氧化氮合酶（nNOS）被急性抑制时，TGF引起的传入小动脉收缩增强，而在nNOS基因敲除小鼠中，TGF保持不变，可能是由于某些未知的适应机制。此外，结果表明，在低钠摄入，致密斑NO的生产增加，从而对抗血管紧张素II（All）的血管收缩作用，并维持肾血流量。3）所有引起的微灌注传入小动脉的血管收缩，通过阻断EET合成增强。阻断AT 2受体可消除这种效应，表明All通过AT 2受体刺激血管扩张剂EET的合成。4）ACE抑制剂诱导细胞色素P450酶表达，从而增强肾脏微粒体组分中20-HETE和EET的合成。这种增强似乎是由ACE通路诱导的组织激肽水平升高介导的。因此，本研究部分阐明了NO、Ado、20-HETE和EE在TGA功能调节中的作用。少

项目成果

Kohagura K, Arima S, Ito S, et al.: "Involvement of cytochrome P450 metabolites in the vascular action of angiotensin II on the afferent arterioles"Hypertens Res.. 24(5). 551-557 (2001)

Kohagura K、Arima S、Ito S 等人：“细胞色素 P450 代谢物参与血管紧张素 II 对传入小动脉的血管作用”Hypertens Res.. 24(5)。

Arima S, Ito S.: "Angiotensin II type 2 receptors in the kidney : evidence for endothelial-cell-mediated renal vasodilatation"Nephrol. Dial. Transplant.. 15. 448-451 (2000)

Arima S、Ito S.：“肾脏中的血管紧张素 II 2 型受体：内皮细胞介导的肾血管舒张的证据”Nephrol。

Ito S.: "Control of afferent and efferent arteriolar tone"Advances in Organ Biology. 9. 63-74 (2000)

Ito S.：“传入和传出小动脉张力的控制”器官生物学进展。

Ito S: "Control of afferent and efferent arteriolar tone"Advances in Organ Biology. 9. 63-74 (2000)

Ito S：“传入和传出小动脉张力的控制”器官生物学进展。

Ohtaka A, Ootak T, Ito S, et al.: "Significance of early phenotypic change of glomerular podocytes detected by Pax2 in primary focal segmental glomerulosclerosis"Am J Kidney Dis. 39. 475-487 (2002)

Ohtaka A、Ootak T、Ito S 等人：“原发性局灶节段性肾小球硬化症中 Pax2 检测到的肾小球足细胞早期表型变化的意义”Am J Kidney Dis。