Renal autoregulation: models combining tubuloglomerular feedback and myogenic response

1987 ◽  
Vol 252 (4) ◽  
pp. F768-F783 ◽  
Author(s):  
K. Aukland ◽  
A. H. Oien
Keyword(s):  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Flow Rate ◽  
Tubuloglomerular Feedback ◽  
Myogenic Response ◽  
Lower Range ◽  
Renal Autoregulation ◽  
Tubular System ◽  
Single Nephron ◽  
Tubular Flow

As shown previously, autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR) at varying arterial pressure may result from a myogenic response (MR) acting to maintain wall tension in each preglomerular vessel segment. We now combine MR with tubuloglomerular feedback (TGF) responding to distal tubular flow rate. The model consists of preglomerular and postglomerular resistances, glomerular filtration, and a tubular system. TGF acting on preglomerular resistance with parameters that mimic responses to single nephron distal tubular flow rate in rats and dogs failed to account for the autoregulation of RBF and GFR observed experimentally. Good autoregulation was obtained by adding preglomerular MR. In this combination, TGF is activated mainly in the lower range of autoregulation. Addition of mechanisms that increase postglomerular resistance or increase the glomerular filtration coefficient at reduced arterial pressure impairs RBF autoregulation, whereas GFR autoregulation is only slightly improved. TGF regulation of pre- and postglomerular resistance in the same direction seems compatible with good autoregulation only when combined with a preglomerular myogenic mechanism.

Model of TGF-proximal tubule interactions in renal autoregulation

1990 ◽  
Vol 259 (4) ◽  
pp. F715-F726 ◽  
Author(s):  
W. A. Cupples ◽  
A. S. Wexler ◽  
D. J. Marsh
Keyword(s):  
Arterial Pressure ◽  
Proximal Tubule ◽  
Flow Rate ◽  
Tubuloglomerular Feedback ◽  
Renal Autoregulation ◽  
Dependent Inhibition ◽  
Arteriolar Resistance ◽  
Tubular Flow ◽  
Renal Blood Flow Autoregulation ◽  
Tubule Fluid

Previous models, assuming constant reabsorption in the proximal tubule, have shown that tubuloglomerular feedback (TGF) can explain only a fraction of glomerular filtration rate (GFR) and renal blood flow autoregulation. Increased arterial pressure inhibits proximal tubule fluid reabsorption, an effect that should increase the efficacy of TGF because of the resulting increased flow rate in the loop of Henle. Models describing pressure and flow in a glomerulus and a nephron were derived to test this prediction. The models were coupled by a TGF function with tubular flow rate at the end of the proximal tubule (superficial nephron) or at the macula densa (juxtamedullary nephron) as input and with afferent arteriolar resistance as output. In agreement withd others, the model predicted that TGF alone could account for about one-half of autoregulation. Pressure-dependent inhibition of proximal reabsorption increased the ability of TGF to account for autoregulation, providing compensation for increases in arterial pressure comparable to published whole kidney values. The inclusion of an approximation of an effect of arterial pressure on TGF marginally improved predicted autoregulation. Although the results suggest that the proximal tubule-TGF interaction can provide a quantitatively adequate explanation for autoregulation, they also indicate that the effect of the interaction is spent at arterial pressures greater than 130 mmHg. Additional mechanisms are required to extend this range.

Feedback mediation of SNGFR autoregulation in hydropenic and DOCA- and salt-loaded rats

1979 ◽  
Vol 237 (1) ◽  
pp. F63-F74 ◽  
Author(s):  
L. C. Moore ◽  
J. Schnermann ◽  
S. Yarimizu
Keyword(s):  
Glomerular Filtration Rate ◽  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Tubuloglomerular Feedback ◽  
Single Nephron ◽  
Proximal Tubular

Tubuloglomerular feedback (TGF) mediation of autoregulation was investigated by measuring the response of single nephron glomerular filtration rate (SNGFR) to changes in arterial pressure (AP) following acute or chronic TGF inhibition. In hydropenic rats with intact TGF, distal SNGFR was 25.0 +/- 1.2 (SE) and 23.9 +/- 1.4 nl/min at AP of 111 and 135 mmHg, respectively. In the same 20 nephrons during proximal tubular microinfusion of furosemide, distal SNGFR was 23.6 +/- 1.4 (n = 16) and 29.7 +/- 1.4 nl/min (n = 20) (P less than 0.001, n = 16) at 112 and 133 mmHg. When determined proximally, SNGFR was 25.6 +/- 1.0 and 29.5 +/- 0.9 nl/min (P less than 0.001, n = 31) at 112 and 157 mmHg; kidney GFR increased similarly. These data and the predictions of a GFR model were then used to estimate autoregulatory efficiency. This analysis indicated that partial autoregulation occurred during TGF inhibition. Therefore, TGF is an essential, but probably not the only, mechanism mediating SNGFR autoregulation.

Tubuloglomerular feedback and SNGFR autoregulation in the rat

1984 ◽  
Vol 247 (2) ◽  
pp. F267-F276 ◽  
Author(s):  
L. C. Moore
Keyword(s):  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Experimental Studies ◽  
Intrinsic Property ◽  
Tubuloglomerular Feedback ◽  
Filtration Pressure ◽  
Single Nephron ◽  
Control System Model ◽  
Additional Support ◽  
Stop Flow

Experimental and simulation studies were undertaken to examine what influence the state of filtration dynamics has on single nephron glomerular filtration rate (SNGFR) autoregulation, to verify the presence of partial autoregulation during tubuloglomerular feedback (TGF) inhibition, and to determine whether small changes in tubular reabsorption could enhance the ability of TGF to regulate SNGFR during autoregulation. The experimental studies in hydropenic rats revealed partial autoregulation of glomerular capillary pressure (using the stop-flow method) and SNGFR during TGF inhibition and complete SNGFR autoregulation with functional TGF. A small significant decrease in fractional volume reabsorption was observed in the distal measurements with increased arterial pressure. Results from a mathematical model of glomerular filtration suggest that SNGFR is inherently more sensitive to changes in arterial pressure in animals exhibiting filtration pressure equilibrium rather than filtration pressure disequilibrium. These data and the simulation results provide additional support for the existence of a TGF-independent autoregulatory mechanism that appears to be an intrinsic property of the preglomerular vasculature. Finally, analysis of autoregulation with a simple control-system model suggests that small changes in proximal tubule or loop of Henle volume reabsorption can provide some or all of the stimulus for TGF activation, thereby significantly increasing the ability of TGF to stabilize SNGFR in response to a rise in arterial pressure.

Renal autoregulation: perspectives from whole kidney and single nephron studies

1978 ◽  
Vol 234 (5) ◽  
pp. F357-F370 ◽  
Author(s):  
L. G. Navar
Keyword(s):  
Glomerular Filtration Rate ◽  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Vascular Resistance ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Distal Nephron ◽  
Renal Autoregulation ◽  
Single Nephron ◽  
Renal Vascular

The phenomenon of renal autoregulation is often thought to relate only to the manner in which the kidney responds to changes in arterial pressure. This review presents a more comprehensive description of the process based on the intrinsic renal vascular responses to changes in arterial pressure, venous pressure, ureteral pressure, and plasma colloid osmotic pressure. Regulation of glomerular filtration rate (GFR), or some function thereof, is the feature most consistently observed. More specifically, in response to external manipulations that change GFR, autonomous changes in renal vascular resistance tend to return GFR back towards normal. The bulk of the evidence suggests that the requisite renal vascular resistance alterations occur predominately at preglomerular segments. Most of the whole kidney autoregulatory responses can be explained on the basis of the distal tubule-glomerular feedback hypothesis, thought to be mediated by the macula densa-juxtaglomerular complex, which states that increases in distal volume delivery lead to increases in afferent arteriolar resistance while reduced distal delivery leads to afferent arteriolar dilation. Micropuncture data have demonstrated that interruption of distal volume delivery prevents single nephrons from autoregulating GFR and glomerular pressure. Also, single nephron glomerular filtration rate (SNGFR) based on proximal collections is higher than SNGFR measured by distal collections or with an indicator-dilution technique. Studies utilized direct microperfusion of the distal nephron from a late proximal tubule site have demonstrated that SNGFR and glomerular pressure decrease in response to increases in distal nephron perfusion rate. Although experiments in rats have been interpreted as indicating that distal chloride concentration and/or reabsorption most likely mediate the feedback responses, recent studies in dogs have demonstrated that feedback responses can be consistently obtained with nonelectrolyte perfusion solutions. These latter studies suggest that the feedback response may be sensitive to some function of total solute delivery or concentration. At present, there is no clear understanding of the intracellular events that link the compositional alterations occurring within the early distal tubule to the final effector system.

Feedback pressure-flow responses in normal and angiotensin-prostaglandin-blocked rats

1984 ◽  
Vol 247 (6) ◽  
pp. F925-F931 ◽  
Author(s):  
A. E. Persson ◽  
L. C. Gushwa ◽  
R. C. Blantz
Keyword(s):  
Flow Rate ◽  
Enzyme Inhibitor ◽  
Tubuloglomerular Feedback ◽  
Maximal Response ◽  
Ang Ii ◽  
Single Nephron ◽  
Proximal Tubular ◽  
Flow Pressure ◽  
Tubular Flow ◽  
Stop Flow

We have examined the response of directly and indirectly (stop-flow) measured glomerular capillary hydrostatic pressure (PGC) and single nephron glomerular filtration rate (SNGFR) to increases in late proximal tubular flow rate in hydropenic rats and rats in which angiotensin II (ANG II) and prostaglandin generation was reduced by 3- to 5-day pretreatment with converting enzyme inhibitor (MK-421) and meclofenamate. In control rats, PGC (48 +/- 2 mmHg) decreased 9 +/- 1 mmHg when 25 nl/min was added to late proximal flow in unobstructed tubules, and PGC decreased 9 +/- 1 mmHg when late proximal perfusion rate was increased from 0 to 40 nl/min, incrementally, in wax-blocked tubules. The turning point or half-maximal response for PGC was at perfusion rates of 23 +/- 2 nl/min. Stop-flow estimated PGC (47 +/- 1 mmHg = control) responses were nearly identical. SNGFR decreased from 30 +/- 1 to 21 +/- 1 nl/min with increased perfusion in control rats. In ANG II-prostaglandin-blocked rats, PGC and stop-flow pressure responses were completely eliminated, yet SNGFR response persisted (36.2 to 28.0 nl/min) but to a somewhat lesser extent. Both direct and indirect PGC decrease with increases in late proximal flow rate in untreated rats. Studies in ANG II-prostaglandin-blocked rats suggest that tubuloglomerular feedback SNGFR responses can occur without changes in PGC, possibly via parallel changes in afferent and efferent arteriolar resistances.

scholarly journals Nitric oxide mediates anomalous tubuloglomerular feedback in rats fed high-NaCl diet after subtotal nephrectomy

2019 ◽  
Vol 316 (2) ◽  
pp. F223-F230 ◽  
Author(s):  
Scott C. Thomson
Keyword(s):  
Nitric Oxide ◽  
Tubuloglomerular Feedback ◽  
Cross Term ◽  
Nitric Oxide Signaling ◽  
Subtotal Nephrectomy ◽  
Single Nephron ◽  
Nos Inhibitor ◽  
Tubular Flow ◽  
Fluid Collections ◽  
Distal Delivery

Tubuloglomerular feedback (TGF) responses become anomalous in rats fed high-NaCl diet after subtotal nephrectomy (STN), such that stimulating TGF causes single nephron GFR (SNGFR) to increase rather than decrease. Micropuncture experiments were performed to determine whether this anomaly results from heightened nitric oxide response to distal delivery, which is a known mechanism for resetting TGF, or from connecting tubule TGF (cTGF), which is a novel amiloride-inhibitable system for offsetting TGF responses. Micropuncture was done in Wistar Froemter rats fed high-NaCl diet (HS) for 8–10 days after STN or sham nephrectomy. TGF was manipulated by orthograde microperfusion of Henle’s loop with artificial tubular fluid with or without NOS inhibitor, LNMMA, or the cell-impermeant amiloride analog, benzamil. SNGFR was measured by inulin clearance in tubular fluid collections from the late proximal tubule. TGF responses were quantified as the increase in SNGFR that occurred when the perfusion rate was reduced from 50 to 8 nl/min in STN or 40 to 8 nl/min in sham animals. The baseline TGF response was anomalous in STN HS (−4 ± 3 vs 14 ± 3 nl/min, P < 0.001). TGF response was normalized by perfusing STN nephron with LNMMA (14 ± 3 nl/min, P < 0.005 for ANOVA cross term) but not with benzamil (−3 ± 4 nl/min, P = 0.4 for ANOVA cross term). Anomalous TGF occurs in STN HS due to heightened effect of tubular flow on nitric oxide signaling, which increases to the point of overriding the normal TGF response. There is no role for cTGF in this phenomenon.

scholarly journals Renal Autoregulation in Health and Disease

2015 ◽  
Vol 95 (2) ◽  
pp. 405-511 ◽  
Author(s):  
Mattias Carlström ◽  
Christopher S. Wilcox ◽  
William J. Arendshorst
Keyword(s):  
Intracellular Signaling ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Tubuloglomerular Feedback ◽  
Free Calcium ◽  
Myogenic Response ◽  
Renal Vasculature ◽  
Renal Autoregulation ◽  
Positive Balance ◽  
Health And Disease

Intrarenal autoregulatory mechanisms maintain renal blood flow (RBF) and glomerular filtration rate (GFR) independent of renal perfusion pressure (RPP) over a defined range (80–180 mmHg). Such autoregulation is mediated largely by the myogenic and the macula densa-tubuloglomerular feedback (MD-TGF) responses that regulate preglomerular vasomotor tone primarily of the afferent arteriole. Differences in response times allow separation of these mechanisms in the time and frequency domains. Mechanotransduction initiating the myogenic response requires a sensing mechanism activated by stretch of vascular smooth muscle cells (VSMCs) and coupled to intracellular signaling pathways eliciting plasma membrane depolarization and a rise in cytosolic free calcium concentration ([Ca2+]i). Proposed mechanosensors include epithelial sodium channels (ENaC), integrins, and/or transient receptor potential (TRP) channels. Increased [Ca2+]ioccurs predominantly by Ca2+influx through L-type voltage-operated Ca2+channels (VOCC). Increased [Ca2+]iactivates inositol trisphosphate receptors (IP3R) and ryanodine receptors (RyR) to mobilize Ca2+from sarcoplasmic reticular stores. Myogenic vasoconstriction is sustained by increased Ca2+sensitivity, mediated by protein kinase C and Rho/Rho-kinase that favors a positive balance between myosin light-chain kinase and phosphatase. Increased RPP activates MD-TGF by transducing a signal of epithelial MD salt reabsorption to adjust afferent arteriolar vasoconstriction. A combination of vascular and tubular mechanisms, novel to the kidney, provides for high autoregulatory efficiency that maintains RBF and GFR, stabilizes sodium excretion, and buffers transmission of RPP to sensitive glomerular capillaries, thereby protecting against hypertensive barotrauma. A unique aspect of the myogenic response in the renal vasculature is modulation of its strength and speed by the MD-TGF and by a connecting tubule glomerular feedback (CT-GF) mechanism. Reactive oxygen species and nitric oxide are modulators of myogenic and MD-TGF mechanisms. Attenuated renal autoregulation contributes to renal damage in many, but not all, models of renal, diabetic, and hypertensive diseases. This review provides a summary of our current knowledge regarding underlying mechanisms enabling renal autoregulation in health and disease and methods used for its study.

Juxtaglomerular interstitial hypertonicity in Amphiuma: tubular origin-TGF signal

1988 ◽  
Vol 254 (3) ◽  
pp. F445-F449 ◽  
Author(s):  
B. E. Persson ◽  
T. Sakai ◽  
D. J. Marsh
Keyword(s):  
Feedback Inhibition ◽  
Distal Tubule ◽  
Juxtaglomerular Apparatus ◽  
Nacl Transport ◽  
Renal Autoregulation ◽  
Rate Dependent ◽  
Single Nephron ◽  
Tubular Flow ◽  
Renal Vascular ◽  
Vascular Autoregulation

One of the mechanisms mediating renal vascular autoregulation in mammals senses tubular flow rate-dependent changes in luminal NaCl concentrations and signals renal arterioles to change diameter. A similar mechanism operates in the salamander, Amphiuma means. To trace the signal, we measured chloride activity in juxtaglomerular interstitial spaces in Amphiuma during perfusion of the early distal tubule belonging to the same nephron. Interstitial Cl- activity exceeded systemic levels and increased when perfusion rate in the adjacent early distal tubule was increased, reaching values more than five times isotonic. Bumetanide, which inhibits NaCl transport by the early distal tubule, eliminated the hypertonicity. Regions of the interstitial space not a part of the juxtaglomerular apparatus (JGA) were not hypertonic. The Cl- concentration was 80% greater than isotonic in the JGA of nephrons studied under free-flow conditions. Single-nephron blood flow, measured by counting the flux of erythrocytes labeled with a fluorescent molecule, showed typical feedback inhibition with maximum sensitivity to the same rates of tubular perfusion that caused the maximum change in JGA interstitial hypertonicity. Juxtaglomerular interstitial hypertonicity could be an important part of the signal for renal autoregulation.

Increased tubuloglomerular feedback activity in Milan hypertensive rats

1986 ◽  
Vol 250 (6) ◽  
pp. F967-F974 ◽  
Author(s):  
U. Boberg ◽  
A. E. Persson
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Tubuloglomerular Feedback ◽  
Spontaneously Hypertensive ◽  
Arterial Blood ◽  
Single Nephron ◽  
Flow Pressure ◽  
Normotensive Strain

Studies of whole-kidney function and micropuncture measurements in superficial nephrons were performed to investigate the role of the tubuloglomerular feedback (TGF) in the excretion of salt and water in hydropenic and volume-expanded rats of the spontaneously hypertensive Milan strain (MHS). The rats were 3.5-5 and 5-7 wk old, and age-matched animals from the Milan normotensive strain (MNS) served as controls. There was no difference in mean arterial blood pressure (Pa) between the 3.5- to 5-wk-old prehypertensive MHS (MHSp) and MNS rats, but the glomerular filtration rate (GFR) was higher in MHSp than in MNS [1.35 vs. 0.80 ml X min-1 X g kidney wt (KW)-1, P less than 0.01]. The distal single-nephron glomerular filtration rate (SNGFR) was also higher in MHSp than in MNS (28.6 vs. 20.2 nl X min-1 X g KW-1, P less than 0.05). TGF was determined from both stop-flow pressure response and proximal and distal SNGFR. It was found that MHSp exhibited essentially no TGF response. During development of hypertension 5- to 7-wk-old MHS (MHSd) had a higher Pa than MNS (120 vs. 98 mmHg, P less than 0.01). Normally GFR and SNGFR increase with age, and such was the case with MNS (0.8 to 1.02 ml X min-1 X g KW-1 and 20.2 to 23.4 nl X min-1 X g KW-1), but in MHSd there was a decrease in both GFR and SNGFR with age (1.35 to 1.10 ml X min-1 X g KW-1 and 28.3 to 18.3 nl X min-1 X g KW-1).(ABSTRACT TRUNCATED AT 250 WORDS)

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