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

肾血流（RBF）保持恒定，尽管肾灌注压（RPP）有很大的变化，这种现象被称为自动调节。肾脏中有两条阻力血管，传入小动脉而非传出小动脉在RPP改变时表现出自调节介导的血管阻力变化。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。肾自身调节是由小管-肾小球反馈（TGF）介导的。TGF是一个稳定RBF、肾小球滤过率（glomerular filtration rate， GFR）和肾小管流速的负反馈系统。RPP的增加通过GFR的增加增加了后期的管状流量。管状流速的增加引起黄斑致密处氯化钠浓度的升高。这是由黄斑致密感觉到的，并导致传入小动脉阻力的增加。本研究的目的是确定更多的内源性物质将信息从黄斑致密作为传感器细胞传递到传入小动脉作为效应器。我们关注腺苷、一氧化氮（NO）和ATP作为可能的候选递质。在以下实验条件下，我们采用微透析技术测量了肾间质中腺苷、ATP或NOx （NO的代谢物）的浓度，并分析了这些物质的浓度与肾血管阻力的关系。1)肾内输注高渗生理盐水导致RBF在短暂升高后降低，间质腺苷浓度显著升高。腺苷1受体拮抗剂完全阻断高渗生理盐水诱导的RBF减少，提示腺苷对TGF的作用。2)在自调节压力范围内RPP的变化对间隙NOx浓度没有影响，但RPP低于自调节压力范围下限时，间隙NOx浓度明显降低。因此，NOx浓度的变化与肾血管阻力之间没有关系。3)与NOx相比，逐步降低RPP可显著降低肾间质ATP浓度，且ATP水平变化与肾血管阻力变化高度相关。进一步的研究表明，乙酰唑胺诱导的远端体积递送增加对TGF的刺激也导致肾间质ATP浓度升高。因此，这些数据清楚地表明，肾间质液中的ATP有助于肾血管阻力的tgf依赖性变化。基于这些发现，我们认为腺苷和ATP在TGF中发挥重要作用，NO可能通过调节多种血管活性物质（包括腺苷和ATP）的作用来促进TGF。少

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