scholarly journals Salt sensitivity of tubuloglomerular feedback in the early remnant kidney

2014 ◽  
Vol 306 (2) ◽  
pp. F172-F180 ◽  
Author(s):  
Prabhleen Singh ◽  
Scott C. Thomson
Keyword(s):  
Tubuloglomerular Feedback ◽  
Distal Nephron ◽  
Fluid Delivery ◽  
Sham Surgery ◽  
Single Nephron ◽  
Flow Pressure ◽  
Nacl Excretion ◽  
Stop Flow ◽  
Remnant Kidney ◽  
Distal Delivery

We previously reported internephron heterogeneity in the tubuloglomerular feedback (TGF) response 1 wk after subtotal nephrectomy (STN), with 50% of STN nephrons exhibiting anomalous TGF (Singh P, Deng A, Blantz RC, Thomson SC. Am J Physiol Renal Physiol 296: F1158–F1165, 2009). Presently, we tested the theory that anomalous TGF is an adaptation of the STN kidney to facilitate increased distal delivery when NaCl balance forces the per-nephron NaCl excretion to high levels. To this end, the effect of dietary NaCl on the TGF response was tested by micropuncture in STN and sham-operated Wistar rats. An NaCl-deficient (LS) or high-salt NaCl diet (HS; 1% NaCl in drinking water) was started on day 0 after STN or sham surgery. Micropuncture followed 8 days later with measurements of single-nephron GFR (SNGFR), proximal reabsorption, and tubular stop-flow pressure (PSF) obtained at both extremes of TGF activation, while TGF was manipulated by microperfusing Henle's loop (LOH) from the late proximal tubule. Activating TGF caused SNGFR to decline by similar amounts in Sham-LS, Sham-HS and STN-LS [ΔSNGFR (nl/min) = −16 ± 2, −11 ± 3, −11 ± 2; P = not significant by Tukey]. Activating TGF in STN-HS actually increased SNGFR by 5 ± 2 nl/min ( P < 0.0005 vs. each other group by Tukey). HS had no effect on the PSF response to LOH perfusion in sham [ΔPSF (mmHg) = −9.6 ± 1.1 vs. −9.8 ± 1.0] but eliminated the PSF response in STN (+0.3 ± 0.9 vs. −5.7 ± 1.0, P = 0.0002). An HS diet leads to anomalous TGF in the early remnant kidney, which facilitates NaCl and fluid delivery to the distal nephron.

Native tubular fluid attenuates ANF-induced inhibition of tubuloglomerular feedback

1990 ◽  
Vol 258 (1) ◽  
pp. F189-F198 ◽  
Author(s):  
D. M. Pollock ◽  
W. J. Arendshorst
Keyword(s):  
Atrial Natriuretic Factor ◽  
Filtration Rate ◽  
Pressure Range ◽  
Tubuloglomerular Feedback ◽  
Fluid Delivery ◽  
Single Nephron ◽  
Proximal Tubular ◽  
Flow Pressure ◽  
Stop Flow

The effect of atrial natriuretic factor [ANF-(1–28); 0.25 microgram.kg-1.min-1] on tubuloglomerular feedback (TGF) and the efficiency of renal blood flow (RBF) autoregulation was determined in anesthetized euvolemic rats. In microperfusion studies, ANF dramatically inhibited (greater than 80%) feedback-mediated decreases in single-nephron glomerular filtration rate (SNGFR) and stop-flow pressure (Psf) when Henle's loop was perfused at 0–48 nl/min with artificial fluid. The sigmoidal relationship between Psf and loop perfusion during control was shifted to a linear relation during ANF; reactivity was almost nonexistent and no inflection point could be discerned. ANF almost completely blocked maximum Psf and SNGFR responses to loop perfusion at rates greater than 24 nl/min. In contrast 30 nl/min loop perfusion with native proximal tubular fluid obtained during ANF infusion restored maximum TGF activity to 70% of control levels. During ANF administration, the paired Psf responses to native and artificial perfusate were significantly different (-5.3 vs. -0.8 mmHg, P less than 0.001), compared with similar responses during control conditions (-7.6 vs. -8.3 mmHg, P greater than 0.1). In free-flow studies, ANF increased proximally and distally measured SNGFR equally. The constancy of the proximal-distal SNGFR difference (10.3 vs. 9.3 nl/min) in the presence of increased distal fluid delivery suggests partial inhibition of TGF during ANF administration. ANF elevated Psf but did not affect basal RBF or the RBF autoregulatory index over an arterial pressure range of 130–70 mmHg. These results indicate that 1) RBF autoregulation is efficiently maintained during ANF infusion when preglomerular vessels are vasodilated and TGF is inhibited by approximately 30%; 2) an endogenous factor(s) in native proximal tubular fluid may attenuate ANF-induced inhibition of TGF; and 3) microperfusion studies using artificial fluid significantly overestimate the net in vivo effect of ANF on TGF.

scholarly journals Natriuretic and Diuretic Actions of a Highly Selective Adenosine A1 Receptor Antagonist

1999 ◽  
Vol 10 (4) ◽  
pp. 714-720
Author(s):  
CHRISTOPHER S. WILCOX ◽  
WILLIAM J. WELCH ◽  
GEORGE F. SCHREINER ◽  
LUIZ BELARDINELLI
Keyword(s):  
Macula Densa ◽  
Tubuloglomerular Feedback ◽  
New Class ◽  
Direct Measurements ◽  
Single Nephron ◽  
A1 Receptor ◽  
Flow Pressure ◽  
Dose Dependent ◽  
Stop Flow ◽  
Distal Delivery

Abstract. The natriuretic and diuretic action of a highly selective adenosine A1 receptor (A1AdoR) antagonist, 1,3-dipropyl-8-[2-(5,6-epoxy)norbornyl]xanthine (CVT-124), was investigated in anesthetized rats. CVT-124 (0.1 to 1 mg/kg) caused dose-dependent increases in urine flow and fractional and absolute sodium excretion of by six- to 10-fold and, at 0.1 mg/kg, increased the GFR (1.6 ± 0.1 to 2.5 ± 0.2 ml/min; P < 0.01). There were no changes in BP or heart rate. CVT-124 reduced absolute proximal reabsorption (26 ± 3 to 20 ± 2 nl/min; P < 0.05) despite unchanged proximally measured, single-nephron GFR (SNGFR) (42 ± 5 to 44 ± 4 nl/min; NS) and thereby decreased fractional proximal reabsorption (60 ± 3 to 46 ± 4%; P < 0.05). Despite increasing distal tubular fluid flow rate (5.4 ± 0.7 to 9.7 ± 0.9 nl/min; P < 0.001), it reduced the proximal-distal difference in SNGFR (before: 9.4 ± 1.0 versus during CVT-124: 4.6 ± 1.5 nl/min; P < 0.01), suggesting that it had blunted the effects of the macula densa on SNGFR. Direct measurements of maximal tubuloglomerular feedback (TGF) responses were made from proximal stop flow pressure (PSF) during orthograde loop perfusion from the proximal tubule with artificial tubular fluid at 40 nl/min. TGF was blunted by intravenous CVT-124 (0.5 mg/kg; ▵PSF with vehicle: 8.3 ± 0.6 versus CVT-124: 6.5 ± 0.3 mmHg; n = 9; P < 0.01). In conclusion, A1AdoR blockade reduces proximal reabsorption and uncouples it from glomerular filtration. It increases distal delivery of fluid yet does not activate a macula densa-dependent fall in SNGFR because it blunts the TGF response. Natriuresis accompanied by blockade of proximal glomerulotubular balance and TGF characterizes a new class of diuretic drugs.

Micropuncture analysis of single-nephron function in NHE3-deficient mice

1999 ◽  
Vol 277 (3) ◽  
pp. F447-F453 ◽  
Author(s):  
John N. Lorenz ◽  
Patrick J. Schultheis ◽  
Timothy Traynor ◽  
Gary E. Shull ◽  
Jürgen Schnermann
Keyword(s):  
Proximal Tubule ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Transport Processes ◽  
Tubuloglomerular Feedback ◽  
Thick Ascending Limb ◽  
Fluid Reabsorption ◽  
Fluid Delivery ◽  
Single Nephron ◽  
Flow Pressure

The Na/H exchanger isoform 3 (NHE3) is expressed in the proximal tubule and thick ascending limb and contributes to the reabsorption of fluid and electrolytes in these segments. The contribution of NHE3 to fluid reabsorption was assessed by micropuncture in homozygous ( Nhe3 −/−) and heterozygous ( Nhe3 +/−) knockout mice, and in their wild-type (WT, Nhe3 +/+) littermates. Arterial pressure was lower in the Nhe3 −/−mice (89 ± 6 mmHg) compared with Nhe3 +/+ (118 ± 4) and Nhe3 +/−(108 ± 5). Collections from proximal and distal tubules demonstrated that proximal fluid reabsorption was blunted in both Nhe3 +/− and Nhe3 −/−mice (WT, 4.2 ± 0.3; Nhe3 +/−, 3.4 ± 0.2; and Nhe3 −/−, 2.6 ± 0.3 nl/min; P < 0.05). However, distal delivery of fluid was not different among the three groups of mice (WT, 3.3 ± 0.4 nl/min; Nhe3 +/−, 3.3 ± 0.2 nl/min; and Nhe3 −/−, 3.0 ± 0.4 nl/min; P < 0.05). In Nhe3 −/−mice, this compensation was largely attributable to decreased single-nephron glomerular filtration rate (SNGFR): 10.7 ± 0.9 nl/min in the Nhe3 +/+ vs. 6.6 ± 0.8 nl/min in the Nhe3 −/−, measured distally. Proximal-distal SNGFR differences in Nhe3 −/−mice indicated that much of the decrease in SNGFR was due to activation of tubuloglomerular feedback (TGF), and measurements of stop-flow pressure confirmed that TGF is intact in Nhe3 −/−animals. In contrast to Nhe3 −/−mice, normalization of early distal flow rate in Nhe3 +/−mice was not related to decreased SNGFR (9.9 ± 0.7 nl/min), but rather, to increased fluid reabsorption in the loop segment ( Nhe3 +/+, 2.6 ± 0.2; Nhe3 +/−, 3.6 ± 0.5 nl/min). We conclude that NHE3 is a major Na/H exchanger isoform mediating Na+ and fluid reabsorption in the proximal tubule. In animals with NHE3 deficiency, normalization of fluid delivery to the distal tubule is achieved through alterations in filtration rate and/or downstream transport processes.

Tubuloglomerular feedback control of distal fluid delivery: effect of extracellular volume

1986 ◽  
Vol 250 (6) ◽  
pp. F1024-F1032 ◽  
Author(s):  
L. C. Moore ◽  
J. Mason
Keyword(s):  
Feedback Loop ◽  
Extracellular Volume ◽  
Extracellular Fluid ◽  
Tubuloglomerular Feedback ◽  
Response Curves ◽  
Fluid Delivery ◽  
Fluid Load ◽  
Single Nephron ◽  
Distal Delivery ◽  
Distal Flow

A closed-feedback loop micropuncture method was used to examine tubuloglomerular feedback (TGF) and the regulation of distal fluid delivery in hydropenic rats (CON), moderately hemorrhaged rats (HEM), and rats given desoxycorticosterone (DOC) and 0.6% saline to drink. Distal delivery and TGF response curves were measured with four samples per nephron: a spontaneous early distal collection, two distal collections during moderate (7.5 nl/min) and saturating (30 nl/min) perturbations in nephron fluid load, and a proximal collection to measure single-nephron glomerular filtration rate (SNGFR) during TGF inhibition. Arterial pressure, predistal volume reabsorption, SNGFR, and early distal flow were significantly higher in DOC than in HEM; the CON group exhibited intermediate values. Except for a greater maximum TGF response in HEM, the normalized TGF responses were similar in all three groups, as was the regulation of distal fluid delivery. However, the TGF onset threshold and the TGF operating point, defined by the spontaneous rates of early distal flow and SNGFR, were reset such that distal fluid delivery and SNGFR were higher in DOC than in HEM, as was renal sodium excretion. The results show that the level around which TGF stabilizes distal fluid delivery is reset when extracellular fluid volume is altered.

TGF-initiated vascular interactions between adjacent nephrons in the rat kidney

1990 ◽  
Vol 259 (1) ◽  
pp. F60-F64 ◽  
Author(s):  
O. Kallskog ◽  
D. J. Marsh
Keyword(s):  
Radial Artery ◽  
Rat Kidney ◽  
Ringer Solution ◽  
Systemic Arterial Pressure ◽  
Tubuloglomerular Feedback ◽  
Lumbar Artery ◽  
Single Nephron ◽  
Flow Pressure ◽  
Pressure Changes ◽  
Stop Flow

We sought to determine whether tubuloglomerular feedback (TGF), activated from one nephron, affects other arterioles derived from the same cortical radial artery. Surface nephrons supplied by a single cortical radial artery were identified by injecting Ringer solution containing Fast Green from a narrow-gauge polyethylene catheter inserted via a lumbar artery into a renal artery. Stop-flow pressure was measured in an identified nephron from such a grouping. In one series, increasing end-proximal flow rate from 0 to 50 nl/min of synthetic tubular fluid in one member of an identified pair of nephrons reduced stop-flow pressure by 1.3 +/- 0.2 mmHg in the other member. When the nephrons were derived from different cortical radial arteries, the stop-flow pressure changed -0.2 +/- 0.1 mmHg. In another series, increasing flow in the adjacent nephron from 0 to 50 nl/min decreased stop-flow pressure 3.9 +/- 0.9 mmHg, and increasing flow in the adjacent nephron by the same amount when flow in the first nephron was 50 nl/min decreased stop-flow pressure 3.4 +/- 0.7 mmHg. These results indicate the operation of an interaction among nephrons derived from a common cortical radial artery. Such an interaction could produce a cooperative effect larger than that predicted from measured single-nephron responses when systemic arterial pressure changes.

scholarly journals A mathematical model of the rat nephron: glucose transport

2015 ◽  
Vol 308 (10) ◽  
pp. F1098-F1118 ◽  
Author(s):  
Alan M. Weinstein
Keyword(s):  
Filtration Rate ◽  
Tubuloglomerular Feedback ◽  
Renal Tubules ◽  
Distal Nephron ◽  
Osmotic Diuresis ◽  
Fluid Delivery ◽  
Glucose Reabsorption ◽  
Sglt2 Inhibition ◽  
Model Equations ◽  
Distal Delivery

Mathematical models of the proximal tubule (PT), loop of Henle (LOH), and distal nephron have been combined to simulate transport by rat renal tubules. The ensemble is composed of 24,000 superficial (SF) nephrons and 12,000 juxtamedullary (JM) nephrons in 5 classes (according to LOH length); all coalesce into 7,200 connecting tubules (CNT). Medullary interstitial solute concentrations are specified. The model equations require that each nephron glomerular filtration rate (GFR) satisfies a tubuloglomerular feedback (TGF) relationship, and each initial hydrostatic pressure yields a common CNT pressure; that common CNT pressure is determined from an overall distal hydraulic resistance to flow. By virtue of the greater GFR for JM nephrons, fluid delivery to SF and JM tubules is comparable. Glucose reabsorption is restricted to the PT, cotransported with one Na in the convoluted tubule (SGLT2), and two Na in the straight tubule (SGLT1). Increasing ambient glucose from 5 to 10 mM increases proximal Na reabsorption and decreases distal delivery. This is mitigated by a TGF-mediated increase in GFR, and may thus be an etiology for TGF-mediated glomerular hyperfiltration. With SGLT2 inhibition by 95%, the model predicts that under normoglycemic conditions about 60% of filtered glucose will still be reabsorbed, so that profound glycosuria is not to be expected. Compared with glucose-driven osmotic diuresis, SGLT2 inhibition provokes greater natriuresis. When hyperglycemia is superimposed on SGLT2 inhibition, the model suggests that natriuresis may be severe, reflecting synergy of a proximal diuretic and osmotic diuresis. In sum, the model captures TGF-mediated diabetic hyperfiltration and predicts glomerular protection with SGLT2 inhibition.

Enhanced tubuloglomerular feedback activity in rats developing spontaneous hypertension

1984 ◽  
Vol 247 (4) ◽  
pp. F672-F679 ◽  
Author(s):  
J. R. Dilley ◽  
W. J. Arendshorst
Keyword(s):  
Arterial Pressure ◽  
Strain Differences ◽  
Tubuloglomerular Feedback ◽  
Adult Rats ◽  
Spontaneously Hypertensive ◽  
Single Nephron ◽  
Flow Through ◽  
Flow Pressure ◽  
Wistar Kyoto ◽  
Stop Flow

Tubular microperfusion was used to evaluate tubuloglomerular feedback (TGF)-mediated changes in single nephron glomerular filtration rate (SNGFR) and stop-flow pressure (SFP) in euvolemic 6- and 11- to 14-wk-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Young SHR compared with WKY had an elevated mean arterial pressure (107 vs. 90 mmHg, P less than 0.001) and a lower proximally measured SNGFR (14 vs. 17 nl/min, P less than 0.001) with no loop perfusion. Perfusion at 32 nl/min produced a greater decrease in SNGFR of SHR (6 vs. 2 nl/min, P less than 0.001). Although basal SFPs were identical (39 mmHg), loop perfusion elicited a greater maximal decline in SFP (-10 vs. -4 mmHg, P less than 0.001) and reactivity of SFP (-1.2 vs. -0.5 mmHg X min X nl-1, P less than 0.001) in young SHR; a lower rate produced a half-maximal decrease in SFP (7 vs. 10 nl/min, P less than 0.02). In adult rats, SNGFRs with no flow through Henle's loop were the same (27 and 28 nl/min) and perfusion at 32 nl/min produced similar decrements in SNGFR (-13 vs. -11 nl/min). The maximal change in SFP was greater in adult SHR (-12 vs. -10 mmHg, P less than 0.02), but there were no strain differences in maximal SFP reactivity (-1.8 vs. -1.3 mmHg X min X nl-1) and the rate eliciting half-maximal SFP changes (12 vs. 12 nl/min). Reduction of arterial pressure to the normotensive range did not alter responses in either age group of SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Tubuloglomerular feedback during elevated renal venous pressure

1985 ◽  
Vol 249 (4) ◽  
pp. F524-F531 ◽  
Author(s):  
U. Boberg ◽  
A. E. Persson
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Volume Expansion ◽  
Filtration Rate ◽  
Venous Pressure ◽  
Tubuloglomerular Feedback ◽  
Interstitial Pressure ◽  
Single Nephron ◽  
Flow Pressure ◽  
Stop Flow

Interstitial hydrostatic and oncotic pressures are believed to influence the sensitivity of the tubuloglomerular feedback (TGF) control. To further investigate this hypothesis, three groups of experiments with elevated renal venous pressure (Prv) were conducted. We investigated 1) the stop-flow pressure (Psf) feedback response; 2) urine flow rate, glomerular filtration rate (GFR), subcapsular interstitial hydrostatic pressure (Psc), and interstitial oncotic pressure (pi int); and 3) the proximal-distal single nephron glomerular filtration rate (SNGFR). The results showed that the Psf feedback response was unaffected by Prv elevation. Psc increased from 0.5 to 3.5 mmHg and pi int increased from 2.1 to 5.8 mmHg; thus, no change in net interstitial pressure (Psc - pi int) was found during elevated Prv. There was a significant proximal-distal SNGFR difference during both control and elevated Prv (8.0 and 6.3 nl/min, respectively). A 20% reduction in total GFR and SNGFR was observed at increased Prv. In separate experiments using the same protocol, a 5% body wt/h volume expansion with saline was induced before Prv was elevated. During volume expansion, TGF sensitivity declined and net interstitial pressure increased, both of which were normalized by increasing Prv. The results show that the TGF sensitivity is normal during elevated Prv to 20 mmHg and that the increase in Psc during this condition is counter-balanced by an increase in pi int. In addition, the decrease in GFR and SNGFR during increased Prv cannot be explained by a change in TGF activity. However, these findings indicate that both interstitial hydrostatic and oncotic pressures may influence the resetting of the TGF sensitivity.

scholarly journals Connecting tubule glomerular feedback mediates tubuloglomerular feedback resetting after unilateral nephrectomy

2018 ◽  
Vol 315 (4) ◽  
pp. F806-F811 ◽  
Author(s):  
Sumit R. Monu ◽  
Yilin Ren ◽  
J. X. Masjoan-Juncos ◽  
Kristopher Kutskill ◽  
Hong Wang ◽  
...  
Keyword(s):  
Indirect Measurement ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Glomerular Injury ◽  
Nacl Transport ◽  
Connecting Tubule ◽  
Flow Pressure ◽  
Stop Flow ◽  
Remnant Kidney ◽  
Epithelial Sodium Channel Enac

Unilaterally nephrectomized rats (UNx) have higher glomerular capillary pressure (PGC) that can cause significant glomerular injury in the remnant kidney. PGC is controlled by the ratio of afferent (Af-Art) and efferent arteriole resistance. Af-Art resistance in turn is regulated by two intrinsic feedback mechanisms: 1) tubuloglomerular feedback (TGF) that causes Af-Art constriction in response to increased NaCl in the macula densa; and 2) connecting tubule glomerular feedback (CTGF) that causes Af-Art dilatation in response to an increase in NaCl transport in the connecting tubule via the epithelial sodium channel (ENaC). Resetting of TGF post-UNx can allow systemic pressure to be transmitted to the glomerulus and cause renal damage, but the mechanism behind this resetting is unclear. Since CTGF is an Af-Art dilatory mechanism, we hypothesized that CTGF is increased after UNx and contributes to TGF resetting. To test this hypothesis, we performed UNx in Sprague-Dawley (8) rats. Twenty-four hours after surgery, we performed micropuncture of individual nephrons and measured stop-flow pressure (PSF). PSF is an indirect measurement of PGC. Maximal TGF response at 40 nl/min was 8.9 ± 1.24 mmHg in sham-UNx rats and 1.39 ± 1.02 mmHg in UNx rats, indicating TGF resetting after UNx. When CTGF was inhibited with the ENaC blocker benzamil (1 μM/l), the TGF response was 12.29 ± 2.01 mmHg in UNx rats and 13.03 ± 1.25 mmHg in sham-UNx rats, indicating restoration of the TGF responses in UNx. We conclude that enhanced CTGF contributes to TGF resetting after UNx.

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