Autoregulatory mechanisms of renal blood flow-Selective responses of afferent arteriole to renal perfusion pressure

肾血流的自身调节机制-传入小动脉对肾灌注压的选择性反应

• 批准号: 11470024
• 负责人: ABE Youichi
• 金额: $ 7.36万
• 依托单位: Kagawa Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470024/
• 关键词: renal autoregulation; tubuloglomenilar feedback; renal interstitium; adenosine; ATP; nitric oxide; microdialvsis; afferent arteriole; 腎微小透析; 腎血流量; サイクリックGMP; アデノシンA_1受容体拮抗薬; 糸球体濾過量; アデノシンA1受容体拮抗薬

Renal blood flow (RBF) remains constant despite wide variations in the renal perfusion pressure (RPP), a phenomenon known as autoregulation. Two resistance vessels are located in the kidney, and afferent arteriole but not efferent arteriole exhibits autoregulation-mediated changes in vascular resistance in response to alterations in RPP. However, it remains to be elucidated why the afferent arteriole selectively responds to the changes in RPP. It is now well established that renal autoregulation is mediated by tubulo-glomerular feedback (TGF). TGF is a negative feedback system that stabilizes RBF, glomerular filtration rate (GFR), and the tubular flow rate. An increase in RPP increases the tubular flow late via an increase in GFR. The increased tubular flow rate causes an elevation of sodium chloride concentration at the macula densa. This is sensed by the macula densa and results in an increase in the afferent arteriolar resistance. The purpose of the present investigation to determin … More e what endogeneous substances transmit information from the macula densa as a sensor cell to the afferent arteriole as an effector. We have focused on an adenosine, nitric oxide (NO) and ATP as possible candidates for the transmitter.We have measured the renal interstitial concentrations of adenosine, ATP or NOx (metabolites of NO) using microdialysis technique at following experimental conditions and analyzed the relations between interstitial concentrations of these substances and renal vascular resistance. 1) The intrarenal infusion of hypertonic saline resulted in a decrease of RBF following a transient increase of RBF and a significant increase of intersitial adenosine concentration. An adenosine 1 receptor antagonist completely blocked the reduction of RBF induced by the hypertonic saline, indicating a role of adenosine for TGF. 2) Changes in RPP within the autoregulatory pressure range did not affect the interstitial concentration of NOx, but the reduction of RPP below than the lower limit of autoregulatory pressure range limit significantly reduced interstitial NOx. Thus, there are no relations between changes in NOx concentration and renal vascular resistance. 3) In contrast to NOx, stepwise reduction of RPP significantly reduced the renal interstitial concentration of ATP arid changes in ATP levels were highly correlated with changes in renal vascular resistance. Further studies demonstrated that stimulation of TGF by increasing distal volume delivery elicited with acetazolamide also led to increases in renal interstitial concentrations of ATP. Thus, these data clearly indicate that ATP in the renal interstitial fluid contribute to the TGF-dependent changes in renal vascular resistance.Based on these findings, we concluded that adenosine and ATP exert significant roles in TGF, and that NO may contribute to TGF via the modulation of the actions of various vasoactive substances including adenosine and ATP. Less

尽管肾灌注压（RPP）变化很大，但肾血流量（RBF）保持恒定，这是一种称为自动调节的现象。两个阻力血管位于肾脏中，并且传入小动脉而不是传出小动脉表现出响应于RPP改变的血管阻力的自动调节介导的变化。然而，为什么传入小动脉选择性地响应RPP的变化仍有待阐明。目前已证实肾自身调节是由肾小管-肾小球反馈（TGF）介导的。TGF是一种负反馈系统，可稳定RBF、肾小球滤过率（GFR）和肾小管流速。RPP的增加通过GFR的增加来增加肾小管流量。肾小管流速增加导致致密斑处氯化钠浓度升高。这被致密斑感觉到，并导致传入小动脉阻力增加。本次调查的目的是确定 ...更多信息 什么样的内源性物质从致密斑作为感受器细胞向作为效应器的传入小动脉传递信息。本研究以腺苷、一氧化氮（NO）和ATP为可能的递质，在以下实验条件下，利用微透析技术测定了肾间质中腺苷、ATP和NOx（NO的代谢产物）的浓度，并分析了这些物质的浓度与肾血管阻力的关系。1)肾内灌注高渗盐水导致RBF降低，随后RBF短暂升高，间质腺苷浓度显著升高。腺苷1受体拮抗剂完全阻断高渗盐水诱导的RBF减少，表明腺苷对TGF的作用。2)在自动调节压力范围内的RPP的变化并不影响氮氧化物的间隙浓度，但低于自动调节压力范围限制的下限的RPP的减少显着减少间隙氮氧化物。因此，NOx浓度的变化与肾血管阻力之间没有关系。3)与NOx相反，RPP的逐步降低显著降低肾间质ATP浓度，并且ATP水平的变化与肾血管阻力的变化高度相关。进一步的研究表明，通过增加乙酰唑胺引起的远端体积递送来刺激TGF也导致肾间质ATP浓度增加。因此，这些数据清楚地表明，ATP在肾间质液有助于TGF-依赖性的肾血管阻力的变化，基于这些发现，我们得出结论，腺苷和ATP发挥重要作用的TGF，和NO可能有助于TGF通过各种血管活性物质，包括腺苷和ATP的调节作用。少

项目成果

Akira Nishiyama et al.: "Renal interstitial adenosine metabolism during ischemia in dogs"Am.J.Physiol.. 280. F231-F238 (2001)

Akira Nishiyama 等：“狗缺血期间的肾间质腺苷代谢”Am.J.Physiol.. 280.F231-F238 (2001)

Y.Fujisawa et al.: "Role of nitric oxide in regulation of renal sympathetic nerve activity during hemorrhage in conscious rats"Am.J.Physiol.. 277. H8-H14 (1999)

Y.Fujisawa 等：“一氧化氮在清醒大鼠出血期间肾交感神经活动调节中的作用”Am.J.Physiol.. 277. H8-H14 (1999)

A. Nishiyama et al.: "Effects of halothane on renal hemodynamics and interstitial nitric oxide in rabbits"Europ. J. Pharmacol.. 367. 299-306 (1999)

A. Nishiyama 等人：“氟烷对兔子肾血流动力学和间质一氧化氮的影响”Europ。

Toshiki Fukui et al.: "Expression of p22-phox and gp91-phox, essential components of NADPH oxidase, increases in infarcted sites of the left ventricle after myocardial infarction."BBRC. in press. (2001)

Toshiki Fukui 等人：“心肌梗塞后左心室梗塞部位的 NADPH 氧化酶的重要成分 p22-phox 和 gp91-phox 的表达增加。”BBRC。

Akira Nishiyama et al.: "Effects of halothane on renal hemodynamics and interstitial nitric oxide in rabbits."Eur.J.Pharmacol.. 367. 299-306 (1999)

Akira Nishiyama 等人：“氟烷对兔子肾血流动力学和间质一氧化氮的影响。”Eur.J.Pharmacol.. 367. 299-306 (1999)