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

尽管肾脏灌注压(RPP)变化很大，但肾血流量(RBF)保持不变，这一现象被称为自动调节。肾内有两条阻力血管，传入小动脉而不是传出小动脉对RPP的改变表现出自动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对RPP的变化作出反应仍有待阐明。现已证实，肾自身调节是由肾小管肾小球反馈(TGF)介导的。转化生长因子是一个稳定RBF、肾小球滤过率(GFR)和肾小管流量的负反馈系统。RPP的增加通过GFR的增加增加了后期的肾小管流量。肾小管流速的增加导致致密黄斑的氯化钠浓度升高。致密黄斑可以感觉到这一点，并导致传入小动脉阻力增加。本次调查的目的是测定…更多的是什么内源性物质将信息从致密黄斑作为感受器细胞传递到作为效应器的传入小动脉。我们重点研究了腺苷、一氧化氮(NO)和三磷酸腺苷(ATP)作为可能的递质递质。在以下实验条件下，我们用微透析技术测量了肾间质中腺苷、三磷酸腺苷或氮氧化物(NO的代谢物)的浓度，并分析了这些物质的间质浓度与肾血管阻力的关系。1)肾内注射高渗盐水后，RBF降低，间质腺苷浓度显著升高。腺苷1受体拮抗剂可完全阻断高渗盐水引起的RBF下降，提示腺苷对转化生长因子的作用。2)RPP在自调节压力范围内的变化对间隙NOx浓度没有影响，但当RPP低于自调节压力范围下限时，间隙NOx显著降低。因此，NOx浓度的变化与肾血管阻力之间没有关系。3)与NOx相反，递减RPP可显著降低肾间质中的ATP浓度，且与肾血管阻力的变化高度相关。进一步的研究表明，乙酰唑胺引起的远端容量递送增加对转化生长因子的刺激也导致肾间质三磷酸腺苷浓度的增加。因此，这些数据清楚地表明，肾间质液中的ATP参与了转化生长因子依赖性的肾血管阻力的改变。根据这些发现，我们得出结论，腺苷和三磷酸腺苷在转化生长因子中发挥重要作用，一氧化氮可能通过调节包括腺苷和三磷酸腺苷在内的多种血管活性物质的作用而参与转化生长因子的形成。较少

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