Tubuloglomerular feedback response in the prenatal and postnatal ovine kidney

2011 ◽  
Vol 300 (6) ◽  
pp. F1368-F1374 ◽  
Author(s):  
Russell D. Brown ◽  
Anita J. Turner ◽  
Mattias Carlström ◽  
A. Erik G. Persson ◽  
Karen J. Gibson
Keyword(s):  
Feedback Mechanism ◽  
Late Gestation ◽  
Tubuloglomerular Feedback ◽  
Maximal Response ◽  
Fetal Life ◽  
Single Nephron ◽  
Developing Kidney ◽  
Tubular Flow ◽  
Arteriolar Tone ◽  
Renal Vascular

The tubuloglomerular feedback mechanism (TGF) plays an important role in regulating single-nephron glomerular filtration rate (GFR) by coupling distal tubular flow to arteriolar tone. It is not known whether TGF is active in the developing kidney or whether it can regulate renal vascular tone and thus GFR during intrauterine life. TGF characteristics were examined in late-gestation ovine fetuses and lambs under normovolemic and volume-expanded (VE) conditions. Lambs and pregnant ewes were anesthetized and the fetuses were delivered via a caesarean incision into a heated water bath, with the umbilical cord intact. Under normovolemic conditions, mean arterial pressure of the fetuses was lower than lambs (51 ± 1 vs. 64 ± 3 mmHg). The maximum TGF response (ΔPSFmax) was found to be lower in fetuses than lambs when tubular perfusion was increased from 0 to 40 nl/min (5.4 ± 0.7 vs. 10.6 ± 0.4 mmHg). Furthermore, the flow rate eliciting half-maximal response [turning point (TP)] was 15.7 ± 0.9 nl/min in fetuses compared with 19.3 ± 1.0 nl/min in lambs, indicating a greater TGF sensitivity of the prenatal kidney. VE decreased ΔPSFmax (4.2 ± 0.4 mmHg) and increased TP to 23.7 ± 1.3 nl/min in lambs. In fetuses, VE increased stop-flow pressure from 26.6 ± 1.5 to 30.3 ± 0.8 mmHg, and reset TGF sensitivity so that TP increased to 21.3 ± 0.7 nl/min, but it had no effect on ΔPSFmax. This study provides direct evidence that the TGF mechanism is active during fetal life and responds to physiological stimuli. Moreover, reductions in TGF sensitivity may contribute to the increase in GFR at birth.

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 after nephron or ureteral obstruction

1985 ◽  
Vol 248 (5) ◽  
pp. F688-F697 ◽  
Author(s):  
G. A. Tanner
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Ureteral Obstruction ◽  
Filtration Rate ◽  
Feedback Mechanism ◽  
Tubuloglomerular Feedback ◽  
Maximal Response ◽  
Single Nephron ◽  
Increased Sensitivity ◽  
Flow Pressure

The effects of 1 day of single nephron, unilateral ureteral (UUO), and bilateral ureteral (BUO) obstruction on tubuloglomerular feedback were studied in anesthetized rats. Stop-flow pressure (SFP) was measured as an index of glomerular capillary pressure before, during, and after loop of Henle microperfusion. Tubuloglomerular feedback (delta SFP) showed an increased sensitivity to low loop perfusion rates and an increased maximal response after 1 day of single nephron obstruction or relief of UUO. Tubuloglomerular feedback was not significantly different from normal after release of BUO. Whole kidney glomerular filtration rate (GFR) was about 10% of normal after release of ureteral obstruction, and single nephron glomerular filtration rate (SNGFR) averaged one-third of normal. Paired measurements of SNGFR from proximal and distal tubules revealed no significant differences in control or in BUO kidneys, but a significant proximal-distal SNGFR difference was observed after UUO. The results suggest that tubuloglomerular feedback does not significantly contribute to the low GFR after release of BUO; after release of UUO, approximately one-fourth of the fall in GFR may be due to activation of the feedback mechanism.

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.

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.

scholarly journals Enhanced tubuloglomerular feedback in mice with vascular overexpression of A1 adenosine receptors

2009 ◽  
Vol 297 (5) ◽  
pp. F1256-F1264 ◽  
Author(s):  
Mona Oppermann ◽  
Yan Qin ◽  
En Yin Lai ◽  
Christoph Eisner ◽  
Lingli Li ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Plasma Renin ◽  
Tubuloglomerular Feedback ◽  
Perfusion Flow ◽  
Enhanced Expression ◽  
Single Nephron ◽  
Basal Plasma ◽  
Actin Promoter ◽  
Afferent Arterioles ◽  
Renal Vascular

Adenosine 1 receptors (A1AR) in the kidney are expressed in the vasculature and the tubular system. Pharmacological inhibition or global genetic deletion of A1AR causes marked reductions or abolishment of tubuloglomerular feedback (TGF) responses. To assess the function of vascular A1AR in TGF, we generated transgenic mouse lines in which A1AR expression in smooth muscle was augmented by placing A1AR under the control of a 5.38-kb fragment of the rat smooth muscle α-actin promoter and first intron ( 12 ). Two founder lines with highest expression in the kidney [353 ± 42 and 575 ± 43% compared with the wild type (WT)] were used in the experiments. Enhanced expression of A1AR at the expected site in these lines was confirmed by augmented constrictor responses of isolated afferent arterioles to administration of the A1AR agonist N6-cyclohexyladenosine. Maximum TGF responses (0–30 nl/min flow step) were increased from 8.4 ± 0.9 mmHg in WT ( n = 21) to 14.2 ± 0.7 mmHg in A1AR-transgene (tg) 4 ( n = 22; P < 0.0001), and to 12.6 ± 1.2 mmHg in A1AR-tg7 ( n = 12; P < 0.02). Stepwise changes in perfusion flow caused greater numerical TGF responses in A1AR-tg than WT in all flow ranges with differences reaching levels of significance in the intermediate flow ranges of 7.5–10 and 10–15 nl/min. Proximal-distal single-nephron glomerular filtration rate (SNGFR) differences (free-flow micropuncture) were also increased in A1AR-tg, averaging 6.25 ± 1.5 nl/min compared with 2.6 ± 0.51 nl/min in WT ( P = 0.034). Basal plasma renin concentrations as well as the suppression of renin secretion after volume expansion were similar in A1AR-tg and WT mice, suggesting lack of transgene expression in juxtaglomerular cells. These data indicate that A1AR expression in vascular smooth muscle cells is a critical component for TGF signaling and that changes in renal vascular A1AR expression may determine the magnitude of TGF responses.

A closed-loop analysis of the tubuloglomerular feedback mechanism

1991 ◽  
Vol 261 (5) ◽  
pp. F880-F889 ◽  
Author(s):  
N. H. Holstein-Rathlou
Keyword(s):  
Flow Rate ◽  
Closed Loop ◽  
Feedback Mechanism ◽  
Open Loop ◽  
Tubuloglomerular Feedback ◽  
Operating Point ◽  
Sprague Dawley ◽  
Loop Analysis ◽  
Experimental Conditions ◽  
Tubular Flow

The tubuloglomerular feedback (TGF) mechanism is of importance in the regulation of glomerular filtration rate (GFR). A second mechanism of potential importance is the change in proximal pressure caused by a change, for example, in the rate of proximal fluid reabsorption. The quantitative contributions of these two mechanisms to the regulation of GFR and the late proximal flow rate are not known. To determine the regulatory efficiency of these two mechanisms, the late proximal flow rate was perturbed by microperfusion with artificial tubular fluid in halothane-anesthetized Sprague-Dawley rats. The resulting changes in late proximal flow rate were measured by pulse injection of rhodamine dextran. Fluorescence was excited by means of a He-Ne laser. Bolus velocity was measured by videomicroscopy. Tubular pressure was measured by the servonulling method. The microperfusion rate was varied from -15 to 20 nl/min in steps of 5 nl/min. The open-loop gain (OLG) was 3.1 (range 1.5-9.9, n = 13) at the unperturbed tubular flow rate, and decreased as the tubular flow rate was either increased or decreased. The proximal pressure increased by 0.21 +/- 0.03 mmHg per unit increase in late proximal flow rate (nl/min). By use of a mathematical model of the glomerulus, it is estimated that under the present experimental conditions the pressure increase contributes 8% (range 3-15%) of the OLG. It is concluded that, for small perturbations around the operating point, TGF accounts for most of the regulation of GFR and the late proximal flow rate, with changes in the proximal pressure of lesser importance. Furthermore, under closed-loop conditions the operating point for the TGF mechanism is at or close to the point of maximal sensitivity.

Tubuloglomerular feedback and blood flow autoregulation during DA1-induced renal vasodilation

1990 ◽  
Vol 258 (3) ◽  
pp. F627-F635 ◽  
Author(s):  
D. M. Pollock ◽  
W. J. Arendshorst
Keyword(s):  
Blood Flow ◽  
Feedback Control ◽  
Arterial Pressure ◽  
Receptor Activation ◽  
Tubuloglomerular Feedback ◽  
Doppler Flowmetry ◽  
Single Nephron ◽  
Electromagnetic Flow Probe ◽  
Induced Changes ◽  
Renal Vascular

The effect of renal vasodilation produced by the dopamine DA1-receptor agonist, fenoldopam (SKF-82526), on tubuloglomerular feedback (TGF) activity and the autoregulation of renal blood flow (RBF) was determined in euvolemic rats. Fenoldopam (2.5 micrograms.kg-1.min-1 iv) increased RBF by 17% (electromagnetic flow probe) while glomerular filtration rate (GFR) was unchanged; mean arterial pressure was decreased by 6%. Superficial cortical blood flow was increased by 12% (laser-Doppler flowmetry) while single-nephron GFR (SNGFR) and estimated glomerular capillary pressure (stop-flow pressure, Psf) were stable. SNGFR measured at proximal and distal sites along the same nephron was not affected by fenoldopam. Partial inhibition of TGF was indicated by the constancy of distal SNGFR and the proximal-distal SNGFR difference in the presence of increased distal delivery of native fluid. However, fenoldopam did not affect feedback control of Psf evaluated by perfusing artificial fluid through Henle's loop at 0-62 nl/min. Despite the decrease in renal vascular resistance over an arterial pressure range of 130 to 70 mmHg, RBF was autoregulated efficiently during fenoldopam infusion. These results indicate that DA1-receptor activation dilates the preglomerular and efferent arterioles without affecting GFR or glomerular pressure. However, this vasodilatory mechanism operates independent of autoregulation and TGF-induced changes in glomerular pressure such that preglomerular vessels remain responsive to the appropriate signals from these intrinsic control systems. The ability of fenoldopam to blunt feedback control of SNGFR may depend on changes in the filtration coefficient independent of glomerular pressure and/or a constituent of natural tubular fluid.

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.

Canine renal vascular response to hyperoncotic dextran in kidneys with or without glomerular filtration

1983 ◽  
Vol 245 (6) ◽  
pp. F687-F690
Author(s):  
R. W. Gotshall
Keyword(s):  
Blood Flow ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Vascular Resistance ◽  
Renal Vascular Resistance ◽  
Tubuloglomerular Feedback ◽  
Vascular Response ◽  
Anesthetized Dogs ◽  
Tubular Flow ◽  
Renal Vascular

The effect of intrarenal arterial infusion of hyperoncotic dextran on renal hemodynamics and excretion was studied in anesthetized dogs. To examine the role of glomerular filtration and tubular flow in the hemodynamic response, several kidney models were employed. Nonfiltering kidneys (NFK) were produced by combined ischemia and ureteral obstruction (UO). Additionally, kidneys with only UO and a lack of filtration as well as kidneys with only ischemia and glomerular filtration were studied. Renal blood flow in normal kidneys was increased by hyperoncotic dextran from 357 +/- 47 to 486 +/- 65 ml X min-1 X 100 g-1, with a corresponding decrease in renal vascular resistance. Ischemic kidneys responded likewise to the dextran infusion, increasing renal blood flow from 261 +/- 31 to 339 +/- 29 ml X min-1 X 100 g-1. Glomerular filtration rate was reduced by the dextran infusion from 80.1 +/- 7.9 to 60.7 +/- 6.6 in normal kidneys and from 31.8 +/- 9.6 to 20.2 +/- 5.8 ml X min-1 X 100 g-1 in ischemic kidneys. Urine flow and sodium excretion were also reduced in these kidneys. In contrast, both NFK and UO, which lacked filtration and tubular flow, did not vasodilate in response to dextran. Renal blood flow remained unchanged from control values (NFK: 146 +/- 6, UO: 111 +/- 22 ml X min-1 X 100 g-1) in these kidneys. These experiments show that the renal vascular response to hyperoncotic dextran is not due to a change in blood volume or viscosity nor to a direct pharmacologic action of dextran. The most likely explanation is that hyperoncotic dextran alters tubuloglomerular feedback control of renal vascular resistance by decreasing filtration and altering tubular flow and/or composition. However, the involvement of another intrarenal vasodilatory system cannot be discounted.

Increased tubular flow induces resetting of tubuloglomerular feedback in euvolemic rats

1996 ◽  
Vol 270 (3) ◽  
pp. F461-F468 ◽  
Author(s):  
S. C. Thomson ◽  
R. C. Blantz ◽  
V. Vallon
Keyword(s):  
Glomerular Filtration Rate ◽  
Volume Expansion ◽  
Filtration Rate ◽  
Tubuloglomerular Feedback ◽  
Optical Technique ◽  
Flow Perturbation ◽  
Single Nephron ◽  
Tubular Flow ◽  
Hormonal Milieu ◽  
Sustained Increase

As single-nephron glomerular filtration rate (SNGFR) and late proximal flow (VLP) increase during growth or following volume expansion, the tubuloglomerular feedback (TGF) function (defined as the decrement in SNGFR due to the process of TGF) shifts rightward in the plane defined by VLP and SNGFR as required to maintain the homeostatic efficiency of TGF. It is not known whether this resetting of TGF requires changes in the systemic hormonal milieu or results from prolonged activation of TGF itself. We employed micropuncture and videometric flow velocitometry (an optical technique for measuring flow in unobstructed nephrons) to address this issue in Inactin-anesthetized euvolemic rats. The fractional compensation (C) of TGF for perturbations [late proximal flow perturbation (VH) = +/- 5 nl/min] in VLP was assessed repeatedly before and during a sustained increase in flow imposed by adding 20 nl/min to early proximal flow (VEP). Augmenting VEP initially saturated TGF, thus suppressing C. Over the next 30 min, C recovered to 70% of its original value, suggesting a rightward resetting of the TGF function to match the increase imposed on VLP. Resetting was confirmed by documenting an evolving asymmetry of C about VH = 0 by testing C vs. VH for -12 < or = VH < or = 12 in increments of 4 nl/min. Beyond 30 min of augmented VEP, C gradually declined due to desensitization of TGF. A sustained increase in VLP is sufficient to include TGF resetting, independent of any change in the systemic neurohumoral milieu.

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