Mechanisms of renal blood flow autoregulation: dynamics and contributions

2007 ◽  
Vol 292 (1) ◽  
pp. R1-R17 ◽  
Author(s):  
Armin Just
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Regulatory Mechanism ◽  
Slow Component ◽  
Tubular Reabsorption ◽  
Tubuloglomerular Feedback ◽  
Ang Ii ◽  
The Third ◽  
Proximal Tubular ◽  
Proximal Tubular Reabsorption

Autoregulation of renal blood flow (RBF) is caused by the myogenic response (MR), tubuloglomerular feedback (TGF), and a third regulatory mechanism that is independent of TGF but slower than MR. The underlying cause of the third regulatory mechanism remains unclear; possibilities include ATP, ANG II, or a slow component of MR. Other mechanisms, which, however, exert their action through modulation of MR and TGF are pressure-dependent change of proximal tubular reabsorption, resetting of RBF and TGF, as well as modulating influences of ANG II and nitric oxide (NO). MR requires < 10 s for completion in the kidney and normally follows first-order kinetics without rate-sensitive components. TGF takes 30–60 s and shows spontaneous oscillations at 0.025–0.033 Hz. The third regulatory component requires 30–60 s; changes in proximal tubular reabsorption develop over 5 min and more slowly for up to 30 min, while RBF and TGF resetting stretch out over 20–60 min. Due to these kinetic differences, the relative contribution of the autoregulatory mechanisms determines the amount and spectrum of pressure fluctuations reaching glomerular and postglomerular capillaries and thereby potentially impinge on filtration, reabsorption, medullary perfusion, and hypertensive renal damage. Under resting conditions, MR contributes ∼50% to overall RBF autoregulation, TGF 35–50%, and the third mechanism < 15%. NO attenuates the strength, speed, and contribution of MR, whereas ANG II does not modify the balance of the autoregulatory mechanisms.

Tubuloglomerular feedback dynamics and renal blood flow autoregulation in rats

1991 ◽  
Vol 260 (1) ◽  
pp. F53-F68 ◽  
Author(s):  
N. H. Holstein-Rathlou ◽  
A. J. Wagner ◽  
D. J. Marsh
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Renal Blood Flow ◽  
Slow Component ◽  
Broad Band ◽  
Experimental Results ◽  
Tubuloglomerular Feedback ◽  
Single Frequency ◽  
Vascular Control ◽  
Arterial Blood

To decide whether tubuloglomerular feedback (TGF) can account for renal autoregulation, we tested predictions of a TGF simulation. Broad-band and single-frequency perturbations were applied to arterial pressure; arterial blood pressure, renal blood flow and proximal tubule pressure were measured. Data were analyzed by linear systems analysis. Broad-band forcings of arterial pressure were also applied to the model to compare experimental results with simulations. With arterial pressure as the input and tubular pressure, renal blood flow, or renal vascular resistance as outputs, the model correctly predicted gain and phase only in the low-frequency range. Experimental results revealed a second component of vascular control active at 100-150 mHz that was not predicted by the simulation. Forcings at single frequencies showed that the system behaves linearly except in the band of 33-50 mHz in which, in addition, there are autonomous oscillations in TGF. Higher amplitude forcings in this band were attenuated by autoregulatory mechanisms, but low-amplitude forcings entrained the autonomous oscillations and provoked amplified oscillations in blood flow, showing an effect of TGF on whole kidney blood flow. We conclude that two components can be detected in the dynamic regulation of renal blood flow, i.e., a slow component that represents TGF and a faster component that most likely represents an intrinsic vascular myogenic mechanism.

A novel mechanism of renal blood flow autoregulation and the autoregulatory role of A1 adenosine receptors in mice

2007 ◽  
Vol 293 (5) ◽  
pp. F1489-F1500 ◽  
Author(s):  
Armin Just ◽  
William J. Arendshorst
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Adenosine Receptors ◽  
Time Course ◽  
Tubuloglomerular Feedback ◽  
The Third ◽  
A1 Adenosine Receptors ◽  
The Impact ◽  
Renal Blood Flow Autoregulation

Autoregulation of renal blood flow (RBF) is mediated by a fast myogenic response (MR; ∼5 s), a slower tubuloglomerular feedback (TGF; ∼25 s), and potentially additional mechanisms. A1 adenosine receptors (A1AR) mediate TGF in superficial nephrons and contribute to overall autoregulation, but the impact on the other autoregulatory mechanisms is unknown. We studied dynamic autoregulatory responses of RBF to rapid step increases of renal artery pressure in mice. MR was estimated from autoregulation within the first 5 s, TGF from that at 5–25 s, and a third mechanism from 25–100 s. Genetic deficiency of A1AR (A1AR−/−) reduced autoregulation at 5–25 s by 50%, indicating a residual fourth mechanism resembling TGF kinetics but independent of A1AR. MR and third mechanism were unaltered in A1AR−/−. Autoregulation in A1AR−/− was faster at 5–25 than at 25–100 s suggesting two separate mechanisms. Furosemide in wild-type mice (WT) eliminated the third mechanism and enhanced MR, indicating TGF-MR interaction. In A1AR−/−, furosemide did not further impair autoregulation at 5–25 s, but eliminated the third mechanism and enhanced MR. The resulting time course was the same as during furosemide in WT, indicating that A1AR do not affect autoregulation during furosemide inhibition of TGF. We conclude that at least one novel mechanism complements MR and TGF in RBF autoregulation, that is slower than MR and TGF and sensitive to furosemide, but not mediated by A1AR. A fourth mechanism with kinetics similar to TGF but independent of A1AR and furosemide might also contribute. A1AR mediate classical TGF but not TGF-MR interaction.

Superficial nephron responses to peritubular capillary infusions of angiotensins I and II

1987 ◽  
Vol 252 (5) ◽  
pp. F818-F824 ◽  
Author(s):  
K. D. Mitchell ◽  
L. G. Navar
Keyword(s):  
Enzyme Inhibitor ◽  
Isotonic Saline ◽  
Tubular Reabsorption ◽  
Ang Ii ◽  
Peritubular Capillary ◽  
Single Nephron ◽  
Proximal Tubular ◽  
Flow Pressure ◽  
Proximal Tubular Reabsorption ◽  
Stop Flow

Proximal tubular reabsorption, stop-flow pressure (SFP), and single nephron glomerular filtration rate (SNGFR) were measured in the absence of and during infusion of an isotonic saline solution containing either angiotensin I (ANG I; 10(-6) to 10(-5) M) or angiotensin II (ANG II; 10(-9) to 10(-7) M) into an adjacent peritubular capillary at a rate of 20 nl/min. Dilution of the infused ANG I and ANG II occurred in the peritubular capillary blood and as the peptides diffused into the interstitium. Infusion of either 10(-7) M ANG II or 10(-5) M ANG I increased proximal fractional fluid reabsorption (FRH2O) and decreased both SFP and SNGFR. There were no significant changes in FRH2O or SNGFR during infusion of 10(-5) M ANG I when the converting enzyme inhibitor enalaprilat (MK 422, 10(-3) M) was added to the infusate. Similarly, peritubular infusion at lower concentrations of either ANG II (10(-9) or 10(-8) M) or ANG I (10(-6) M) did not alter FRH2O, SFP, or SNGFR. These data indicate that conversion of ANG I to ANG II can occur in the peritubular capillary or interstitial environment and that increases above the normal endogenous levels in the postglomerular interstitial ANG II concentration can enhance proximal tubular reabsorption and increase preglomerular resistance and thereby reduce SNGFR.

Dynamics and contribution of mechanisms mediating renal blood flow autoregulation

2003 ◽  
Vol 285 (3) ◽  
pp. R619-R631 ◽  
Author(s):  
Armin Just ◽  
William J. Arendshorst
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Response Times ◽  
Slow Component ◽  
Regulatory System ◽  
Tubuloglomerular Feedback ◽  
Maximum Speed ◽  
Myogenic Response ◽  
Total Response ◽  
Relative Contribution

We investigated dynamic characteristics of renal blood flow (RBF) autoregulation and relative contribution of underlying mechanisms within the autoregulatory pressure range in rats. Renal arterial pressure (RAP) was reduced by suprarenal aortic constriction for 60 s and then rapidly released. Changes in renal vascular resistance (RVR) were assessed following rapid step reduction and RAP rise. In response to rise, RVR initially fell 5-10% and subsequently increased ∼20%, reflecting 93% autoregulatory efficiency (AE). Within the initial 7-9 s, RVR rose to 55% of total response providing 37% AE, reaching maximum speed at 2.2 s. A secondary RVR increase began at 7-9 s and reached maximum speed at 10-15 s. Response times suggest that the initial RVR reflects the myogenic response and the secondary tubuloglomerular feedback (TGF). During TGF inhibition by furosemide, AE was 64%. The initial RVR rise was accelerated and enhanced, providing 49% AE, but it represented only 88% of total. The remaining 12% indicates a third regulatory component. The latter contributed up to 50% when the RAP increase began below the autoregulatory range. TGF augmentation by acetazolamide affected neither AE nor relative myogenic contribution. Diltiazem infusion markedly inhibited AE and the primary and secondary RVR increases but left a slow component. In response to RAP reduction, initial vasodilation constituted 73% of total response but was not affected by furosemide. The third component's contribution was 9%. Therefore, RBF autoregulation is primarily due to myogenic response and TGF, contributing 55% and 33-45% in response to RAP rise and 73% and 18-27% to RAP reduction. The data imply interaction between TGF and myogenic response affecting strength and speed of myogenic response during RAP rises. The data suggest a third regulatory system contributing <12% normally but up to 50% at low RAP; its nature awaits further investigation.

High-NaCl intake impairs dynamic autoregulation of renal blood flow in ANG II-infused rats

2010 ◽  
Vol 299 (5) ◽  
pp. R1142-R1149 ◽  
Author(s):  
Aso Saeed ◽  
Gerald F. DiBona ◽  
Niels Marcussen ◽  
Gregor Guron
Keyword(s):  
Blood Flow ◽  
Transfer Function ◽  
Renal Blood Flow ◽  
Function Analysis ◽  
Feedback Mechanism ◽  
Tubuloglomerular Feedback ◽  
Ang Ii ◽  
Frequency Range ◽  
Sprague Dawley ◽  
Transfer Function Analysis

The aim of this study was to investigate dynamic autoregulation of renal blood flow (RBF) in ANG II-infused rats and the influence of high-NaCl intake. Sprague-Dawley rats received ANG II (250 ng·kg−1·min−1 sc) or saline vehicle (sham) for 14 days after which acute renal clearance experiments were performed during thiobutabarbital anesthesia. Rats ( n = 8–10 per group) were either on a normal (NNa; 0.4% NaCl)- or high (HNa; 8% NaCl)-NaCl diet. Separate groups were treated with 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol; 1 M in drinking water). Transfer function analysis from arterial pressure to RBF in the frequency domain was used to examine the myogenic response (MR; 0.06–0.09 Hz) and the tubuloglomerular feedback mechanism (TGF; 0.03–0.06 Hz). MAP was elevated in ANG II-infused rats compared with sham groups ( P < 0.05). RBF in ANG II HNa was reduced vs. sham NNa and sham HNa (6.0 ± 0.3 vs. 7.9 ± 0.3 and 9.1 ± 0.3 ml·min−1·g kidney wt−1, P < 0.05). transfer function gain in ANG II HNa was significantly elevated in the frequency range of the MR (1.26 ± 0.50 dB, P < 0.05 vs. all other groups) and in the frequency range of the TGF (−0.02 ± 0.50 dB, P < 0.05 vs. sham NNa and sham HNa). Gain values in the frequency range of the MR and TGF were significantly reduced by tempol in ANG II-infused rats on HNa diet. In summary, the MR and TGF components of RBF autoregulation were impaired in ANG II HNa, and these abnormalities were attenuated by tempol, suggesting a pathogenetic role for superoxide in the impaired RBF autoregulatory response.

scholarly journals Detection of low-frequency oscillations in renal blood flow

2009 ◽  
Vol 297 (1) ◽  
pp. F155-F162 ◽  
Author(s):  
K. L. Siu ◽  
B. Sung ◽  
W. A. Cupples ◽  
L. C. Moore ◽  
K. H. Chon
Keyword(s):  
Blood Flow ◽  
Transfer Function ◽  
Renal Blood Flow ◽  
Experimental Approach ◽  
Low Frequency ◽  
Tubuloglomerular Feedback ◽  
Resonant Peak ◽  
The Third ◽  
Transfer Function Analysis ◽  
Autoregulatory Mechanism

Detection of the low-frequency (LF; ∼0.01 Hz) component of renal blood flow, which is theorized to reflect the action of a third renal autoregulatory mechanism, has been difficult due to its slow dynamics. In this work, we used three different experimental approaches to detect the presence of the LF component of renal autoregulation using normotensive and spontaneously hypertensive rats (SHR), both anesthetized and unanesthetized. The first experimental approach utilized a blood pressure forcing in the form of a chirp, an oscillating perturbation with linearly increasing frequency, to elicit responses from the LF autoregulatory component in anesthetized normotensive rats. The second experimental approach involved collection and analysis of spontaneous blood flow fluctuation data from anesthetized normotensive rats and SHR to search for evidence of the LF component in the form of either amplitude or frequency modulation of the myogenic and tubuloglomerular feedback mechanisms. The third experiment used telemetric recordings of arterial pressure and renal blood flow from normotensive rats and SHR for the same purpose. Our transfer function analysis of chirp signal data yielded a resonant peak centered at 0.01 Hz that is greater than 0 dB, with the transfer function gain attenuated to lower than 0 dB at lower frequencies, which is a hallmark of autoregulation. Analysis of the data from the second experiments detected the presence of ∼0.01-Hz oscillations only with isoflurane, albeit at a weaker strength compared with telemetric recordings. With the third experimental approach, the strength of the LF component was significantly weaker in the SHR than in the normotensive rats. In summary, our detection via the amplitude modulation approach of interactions between the LF component and both tubuloglomerular feedback and the myogenic mechanism, with the LF component having an identical frequency to that of the resonant gain peak, provides evidence that 0.01-Hz oscillations may represent the third autoregulatory mechanism.

l-arginine-induced glomerular hyperfiltration response: the roles of insulin and ANG II

2008 ◽  
Vol 294 (5) ◽  
pp. R1744-R1751 ◽  
Author(s):  
Mario Ruiz ◽  
Prabhleen Singh ◽  
Scott C. Thomson ◽  
Karen Munger ◽  
Roland C. Blantz ◽  
...  
Keyword(s):  
Glomerular Filtration ◽  
Insulin Release ◽  
Insulin Infusion ◽  
Tubuloglomerular Feedback ◽  
Ang Ii ◽  
Insulin Levels ◽  
Single Nephron ◽  
Proximal Tubular ◽  
Underlying Mechanisms ◽  
Proximal Tubular Reabsorption

Infusion of l-arginine produces an increase in glomerular filtration via kidney vasodilation, correlating with increased kidney excretion of nitric oxide (NO) metabolites, but the specific underlying mechanisms are unknown. We utilized clearance and micropuncture techniques to examine the whole kidney glomerular filtration rate (GFR) and single nephron GFR (SNGFR) responses to 1) l-arginine (ARG), 2) ARG+octreotide (OCT) to block insulin release, 3) ARG+OCT+insulin (INS) infusion to duplicate ARG-induced insulin levels, and 4) losartan (LOS), an angiotensin AT-1 receptor blocker, +ARG+OCT. ARG infusion increased GFR, while increasing insulin levels. OCT coinfusion prevented this increase in GFR, but with insulin infusion to duplicate ARG induced rise in insulin, the GFR response was restored. Identical insulin levels in the absence of ARG had no effect on GFR. In contrast to ARG infusion alone, coinfusion of OCT with ARG reduced proximal tubular fractional and absolute reabsorption potentially activating tubuloglomerular feedback. Losartan infusion, in addition to ARG and OCT (LOS+ARG+OCT), restored the increase in both SNGFR and proximal tubular reabsorption, without increasing insulin levels. In conclusion, 1) hyperfiltration responses to ARG require the concurrent, modest, permissive increase in insulin; 2) inhibition of insulin release after ARG reduces proximal reabsorption and prevents the hyperfiltration response; and 3) inhibition of ANG II activity restores the hyperfiltration response, maintains parallel increases in proximal reabsorption, and overrides the arginine/octreotide actions.

Homeostatic efficiency of tubuloglomerular feedback is reduced in established diabetes mellitus in rats

1995 ◽  
Vol 269 (6) ◽  
pp. F876-F883 ◽  
Author(s):  
V. Vallon ◽  
R. C. Blantz ◽  
S. Thomson
Keyword(s):  
Streptozotocin Diabetes ◽  
Diabetic Rats ◽  
Tubular Reabsorption ◽  
Tubuloglomerular Feedback ◽  
Ambient Flow ◽  
Proximal Tubular ◽  
On Line ◽  
Tubular Flow ◽  
A Minor ◽  
Proximal Tubular Reabsorption

We tested the hypothesis that the ability of the tubuloglomerular feedback (TGF) to stabilize renal function is impaired in rats with 7-8 wk of insulin-treated streptozotocin-diabetes. Proximal tubular flow was measured in free-flowing nephrons using a noninvasive optical technique. The homeostatic efficiency of TGF was determined from the fractional compensation for perturbations in ambient flow. Fractional compensation was substantially reduced in diabetic rats. To assess the roles of the proximal tubule and loop of Henle as determinants of TGF efficiency, we tested the effect of diabetes on proximal tubular reabsorption as determined by standard micropuncture and on the ionic content of early distal tubular fluid by employing a microelectrode for on-line measurement of electrical conductivity (TED). Diabetes caused glomerular hyperfiltration and increased fractional proximal tubular reabsorption (FPR), such that late proximal tubular flow (VLP) and early distal tubular flow were unaffected. The increase in FPR was a minor contributor to the overall effect on fractional compensation. Diabetes decreased the ambient TED without affecting the slope of the relationship between VLP and TED. These results demonstrate that the homeostatic, efficiency of the TGF system is reduced in diabetes and that this cannot be fully accounted for by changes in tubular reabsorption. Impaired TGF efficiency renders the diabetic glomerular microvasculature more susceptible to impact from fluctuations in systemic hemodynamics.

Atrial natriuretic factor, angiotensin II, and the slow component of renal autoregulation

1994 ◽  
Vol 72 (10) ◽  
pp. 1132-1137 ◽  
Author(s):  
Raouf E. Naguib ◽  
Chantal Contant ◽  
W. A. Cupples
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Renal Blood Flow ◽  
Atrial Natriuretic Factor ◽  
Perfusion Pressure ◽  
Slow Component ◽  
Tubuloglomerular Feedback ◽  
Time Constants ◽  
Renal Autoregulation ◽  
Resistance Vessels

Autoregulation of renal blood flow is highly efficient and is mediated partly by tubuloglomerular feedback (TGF), which couples regulation of blood flow to that of sodium excretion. Atrial natriuretic factor (ANF) dilates preglomerular resistance vessels, in which autoregulation occurs, and has been reported to inhibit TGF. This study addressed potential actions of ANF on the slow, TGF-mediated, component of autoregulation. Renal blood flow was measured by an electromagnetic flow probe in Sprague – Dawley rats anesthetized by halothane or isoflurane while renal perfusion pressure was manipulated by a servo-controlled clamp placed on the aorta between the renal arteries. Progressive reduction of perfusion pressure to 60 mmHg (1 mmHg = 133.3 Pa) induced resetting of autoregulation to operate at the reduced pressure and to defend lower renal blood flow. Infusion of ANF at a dose shown to reliably increase sodium excretion did not affect autoregulation or its resetting. Because resetting is angiotensin II dependent, the converting enzyme inhibitor Enalaprilat® was used to provide angiotensin II blockade. As expected, autoregulation did not reset to operate at reduced perfusion pressure. Again ANF was without effect. In a third experiment, relaxation of resistance was assessed in response to repeated steps of perfusion pressure between 65 and 75 mmHg. Time constants of constriction and dilatation were recovered by fitting to a single exponential before and during ANF infusion. Time constants ranged from 0.045 to 0.055 Hz, were consistent with operation of TGF, were not different for constriction or dilatation, and were unaltered by ANF; nor did ANF affect the magnitude of constriction or dilatation. Autoregulation compensated for ≈ 87% of the increase and ≈ 79% of the decrease in driving pressure during control. During ANF infusion it compensated for ≈ 98% of the increase and ≈ 82% of the decrease. The results indicate that, although ANF and angiotensin II act on the same resistance vessels, ANF does not attenuate angiotensin II dependent resetting of renal autoregulation; nor does ANF inhibit the slow component of renal autoregulation.Key words: resistance, tubuloglomerular feedback, time constant.

Renal blood flow, early distal sodium, and plasma renin concentrations during osmotic diuresis

2000 ◽  
Vol 279 (4) ◽  
pp. R1268-R1276 ◽  
Author(s):  
Paul P. Leyssac ◽  
Niels-Henrik Holstein-Rathlou ◽  
Ole Skøtt
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Sodium Excretion ◽  
Plasma Renin ◽  
Urine Flow ◽  
Sodium Reabsorption ◽  
Osmotic Diuresis ◽  
Nacl Concentration ◽  
Proximal Tubular ◽  
Distal Tubules

Inconsistencies in previous reports regarding changes in early distal NaCl concentration (EDNaCl) and renin secretion during osmotic diuresis motivated our reinvestigation. After intravenous infusion of 10% mannitol, EDNaCl fell from 42.6 to 34.2 mM. Proximal tubular pressure increased by 12.6 mmHg. Urine flow increased 10-fold, and sodium excretion increased by 177%. Plasma renin concentration (PRC) increased by 58%. Renal blood flow and glomerular filtration rate decreased, however end-proximal flow remained unchanged. After a similar volume of hypotonic glucose (152 mM), EDNaClincreased by 3.6 mM, ( P < 0.01) without changes in renal hemodynamics, urine flow, sodium excretion rate, or PRC. Infusion of 300 μmol NaCl in a smaller volume caused EDNaCl to increase by 6.4 mM without significant changes in PRC. Urine flow and sodium excretion increased significantly. There was a significant inverse relationship between superficial nephron EDNaCl and PRC. We conclude that EDNa decreases during osmotic diuresis, suggesting that the increase in PRC was mediated by the macula densa. The results suggest that the natriuresis during osmotic diuresis is a result of impaired sodium reabsorption in distal tubules and collecting ducts.

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