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

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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