The effect of tubular perfusion with PGE2, PGF2α, and PGI2 on the tubuloglomerular feedback control in the rat

1983 ◽  
Vol 61 (11) ◽  
pp. 1317-1323 ◽  
Author(s):  
A. Erik G. Persson ◽  
Bengt Hahne ◽  
Göran Selén
Keyword(s):  
Control Level ◽  
Renal Medulla ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Perfusion Solution ◽  
Sprague Dawley Rats ◽  
Feedback Sensitivity ◽  
Proximal Tubular ◽  
Flow Pressure ◽  
Tubular Flow

The prostaglandins (PG) of the renal medulla might affect the nephron and the cortical arteriolar function via the tubular route. To investigate this question PGE2 (1 μg/mL), PGF2α (10 μg/mL), or PGI2 (1 ng/mL) was added to the tubular perfusion solution when the characteristics of the tubuloglomerular feedback (TGF) control were measured. The experiments were performed on Sprague–Dawley rats. The proximal tubular stop-flow pressure (PSF) was measured upstream to a wax block, while at the same time the distal nephron was perfused with prostaglandin-containing or prostaglandin-free solutions at different flow rates varying from 0 to 50 nL/min. The maximal drop in PSF (ΔPSF) and the tubular flow rate at which 50% of the ΔPSF response was obtained, the turning point (TP), were determined. When PGE2 or PGF2α was added to the tubular perfusion solution in the control animals a significant increase in feedback sensitivity was found. After 10 min of tubular PGI2 perfusion the feedback sensitivity was almost completely abolished, with a ΔPSF of 0.8 mmHg (1 mmHg = 133.322 Pa) (control 8.4 mmHg) and a TP of >40 nL/min (control 22 nL/min). After nephrectomy the feedback sensitivity was reduced, with a ΔPSF of 2.0 mmHg and a TP of >40 nL/min. When PGE2 was added to the tubular perfusion solution in the uninephrectomized animals, the feedback sensitivity was increased to the control level, with a ΔPSF of 8.2 mmHg and a TP of 20.0 nL/min. The results show that PGI2 reduces and PGE2 and PGF2α increase TGF sensitivity when added to the tubular perfusion solution and that the decrease seen after nephrectomy is again reset to the control level by intratubular PGE2 administration.

scholarly journals Resetting of exaggerated tubuloglomerular feedback activity in acutely volume-expanded young SHR

1999 ◽  
Vol 276 (3) ◽  
pp. F409-F416 ◽  
Author(s):  
Kristina Brännström ◽  
William J. Arendshorst
Keyword(s):  
Turning Point ◽  
Tubuloglomerular Feedback ◽  
Maximal Response ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Sprague Dawley Rats ◽  
Proximal Tubular ◽  
Wistar Kyoto ◽  
Tubular Flow

One purpose of the present study was to evaluate the ability of 7-wk-old spontaneously hypertensive rats (SHR) to reset tubuloglomerular feedback (TGF) activity in response to acute volume expansion (VE). Second, we evaluated the contribution of ANG II, via its action on AT1 receptors, to TGF control of glomerular function during VE. TGF was assessed by micropuncture methods and proximal tubular stop-flow pressure (SFP) determinations in SHR, Wistar-Kyoto rats (WKY), and Sprague-Dawley rats (SD). During euvolemia SHR exhibited enhanced TGF activity. In the same animals acute VE was achieved by infusion of saline (5 ml ⋅ h−1 ⋅ 100 g body wt−1). VE led to resetting of TGF in all three strains. Maximal SFP responses, elicited by a 30–40 nl/min loop of Henle perfusion rate, decreased from 19 to 12 mmHg in SHR and, on average, from 11 to 5 mmHg in WKY and SD ( P < 0.001). Tubular flow rate producing a half-maximal response (turning point) shifted to higher flow rates during VE, from 12 to 14 nl/min in SHR and from 15 to 19 nl/min in WKY. Administration of the AT1 receptor blocker candesartan (0.05 mg/kg iv) during sustained VE decreased TGF-mediated reductions in SFP in SHR and slightly increased the turning point in WKY. Nevertheless, other parameters of TGF activity were unaffected by AT1 receptor blockade. In conclusion, young SHR possess the ability to reset TGF activity in response to VE to a degree similar to compensatory adjustments in WKY. However, TGF remains enhanced in SHR during VE. ANG II and its action on AT1 receptors are in part responsible for the exaggerated SFP responses in young SHR during VE.

Tubuloglomerular feedback and tubular reabsorption during acute potassium loading in rats

1994 ◽  
Vol 267 (2) ◽  
pp. F223-F230 ◽  
Author(s):  
B. Braam ◽  
P. Boer ◽  
H. A. Koomans
Keyword(s):  
Distal Tubule ◽  
Plasma Potassium ◽  
Tubuloglomerular Feedback ◽  
Control Group ◽  
Sprague Dawley ◽  
Time Control ◽  
Sprague Dawley Rats ◽  
Single Nephron ◽  
Flow Pressure ◽  
Potassium Loading

Acute hyperkalemia has been associated with changes in reabsorption, glomerular filtration rate (GFR), and autoregulation, which might represent altered tubuloglomerular feedback (TGF) responsiveness. Therefore, TGF responsiveness, segmental reabsorption of water, sodium and potassium, and single-nephron GFR were evaluated during acute potassium loading in male Sprague-Dawley rats. Rats receiving 300 mM KNO3, KHCO3, and KCl showed significantly increased plasma potassium levels and attenuation of stop-flow pressure responses 45-90 min after starting the potassium infusion compared with that observed in time controls and rats infused with 300 mM NaCl. Attenuation of TGF responsiveness could not be related to plasma and kidney angiotensin II levels. Segmental water and sodium handling and proximal to distal single-nephron GFR differences assessed in a time control group and a group receiving 300 mM KCl revealed no changes related to KCl infusion. However, late proximal and early distal potassium concentrations increased significantly from 4.7 +/- 0.2 to 6.3 +/- 0.3 mM (P < 0.01) and from 1.5 +/- 0.1 to 2.7 +/- 0.4 mM (P < 0.01), respectively. In summary, although attenuated TGF responsiveness was demonstrated at higher perfusion rates, this study does not support a significant role for either the TGF mechanism or changes in reabsorption upstream of the early distal tubule for the initiation of kaliuresis during acute potassium loading.

scholarly journals Testosterone enhances tubuloglomerular feedback by increasing superoxide production in the macula densa

2013 ◽  
Vol 304 (9) ◽  
pp. R726-R733 ◽  
Author(s):  
Yiling Fu ◽  
Yan Lu ◽  
Eddie Y. Liu ◽  
Xiaolong Zhu ◽  
Gouri J. Mahajan ◽  
...  
Keyword(s):  
Macula Densa ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Mediated Effects ◽  
Sprague Dawley Rats ◽  
Flow Pressure ◽  
Laser Capture ◽  
Stop Flow ◽  
Dependent Pathway

Males have higher prevalence of hypertension and renal injury than females, which may be attributed in part to androgen-mediated effects on renal hemodynamics. Tubuloglomerular feedback (TGF) is an important mechanism in control of renal microcirculation. The present study examines the role of testosterone in the regulation of TGF responses. TGF was measured by micropuncture (change of stop-flow pressure, ΔPsf) in castrated Sprague-Dawley rats. The addition of testosterone (10−7 mol/l) into the lumen increased the ΔPsf from 10.1 ± 1.2 to 12.2 ± 1.2 mmHg. To determine whether androgen receptors (AR) are involved, mRNA of AR was measured in the macula dense cells isolated by laser capture microdissection from kidneys, and a macula densa-like cell line (MMDD1). AR mRNA was expressed in the macula densa of rats and in MMDD1 cells. We next examined the effects of the AR blocker, flutamide (10−5 mol/l) on the TGF response. The addition of flutamide blocked the effects of testosterone on TGF. The addition of Tempol (10−4 mol/l) or polyethylene glycol-superoxide dismutase (100 U/ml) to scavenge superoxide blocked the effect of testosterone to augment TGF. We then applied apocynin to inhibit NAD(P)H oxidase and oxypurinol to inhibit xanthine oxidase and found the testosterone-induced augmentation of TGF was blocked. In additional experiments in MMDD1 cells, we found that testosterone increased O2− generation. Apocynin or oxypurinol blocked the testosterone-induced increases of O2−, while blockade of COX-2 with NS-398 had no effect. These findings suggest that testosterone enhances TGF response by stimulating O2− production in macula densa via an AR-dependent pathway.

Oscillations of tubular pressure, flow, and distal chloride concentration in rats

1989 ◽  
Vol 256 (6) ◽  
pp. F1007-F1014 ◽  
Author(s):  
N. H. Holstein-Rathlou ◽  
D. J. Marsh
Keyword(s):  
Flow Rate ◽  
Fluid Velocity ◽  
Chloride Concentration ◽  
Feedback Mechanism ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Mean Values ◽  
Sprague Dawley Rats ◽  
Proximal Tubular ◽  
Chloride Activity

Previous experiments have shown oscillations in proximal tubular pressure in halothane-anesthetized rats. Such oscillations should be due to oscillations in flow rate and should cause periodic oscillations in both distal tubular chloride concentration and distal tubular pressure. The purpose of the study was to test these predictions. In halothane-anesthetized Sprague-Dawley rats, distal tubular chloride activity was measured with Cl- -sensitive electrodes, and late proximal flow rate was measured by pulse injection of boluses of solutions containing rhodamine dextran. Bolus velocity was detected by videomicroscopy. The time resolution was 2 s. All four variables oscillated with the same frequency, approximately 35 mHz. The amplitude of the flow and the chloride oscillations were 28 and 10%, respectively, of the mean values. Proximal fluid velocity led proximal pressure by 1.5 +/- 0.4 s, whereas distal chloride activity lagged proximal pressure by 8.9 +/- 0.8 s. The distal pressure lagged the proximal pressure by 1.05 +/- 0.38 s. It is concluded that there is a significant variation in distal chloride activity, the magnitude of which appears to be sufficient to account for the observed flow variations through the operation of the tubuloglomerular feedback mechanism.

scholarly journals Nitric oxide release as an essential mitigating step in tubuloglomerular feedback: observations during intrarenal nitric oxide clamp.

1998 ◽  
Vol 9 (9) ◽  
pp. 1596-1603
Author(s):  
E Turkstra ◽  
B Braam ◽  
H A Koomans
Keyword(s):  
Nitric Oxide ◽  
Macula Densa ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Arginine Infusion ◽  
Nitric Oxide Release ◽  
Sprague Dawley Rats ◽  
Flow Pressure ◽  
Oxide Synthase ◽  
Nitroprusside Infusion

Nitric oxide synthase inhibition in the kidney enhances tubuloglomerular feedback (TGF) responsiveness. This may reflect either the effect of reduced basal nitric oxide (NO) availability or the effect of impaired NO release that is physiologically induced by TGF activation. However, it is unknown whether the latter actually takes place. In this study, it was hypothesized that NO is released (from macula densa cells or endothelium) as part of the normal TGF loop, and mitigates the TGF response. In Sprague Dawley rats, TGF responsiveness was assessed (fall in tubular stop flow pressure, deltaSFP, upon switching loop of Henle perfusion rates from 0 to 40 nl/min) during an intrarenal NO clamp (systemic infusion of nitro-L-arginine, 10 microg/kg per min, followed by intrarenal nitroprusside infusion adjusted to restore renal blood flow [RBF]). This maneuver was presumed to fix intrarenal NO impact at a physiologic level. To validate the approach, TGF responsiveness during an intrarenal angiotensin II (AngII) clamp (systemic infusion of enalaprilat 0.2 mg/kg per min, followed by intrarenal AngII infusion) was also studied. AngII is presumed to modulate but not mediate, TGF, thus not to increase as part of the TGF loop. In untreated animals, RBF was 7.4 +/- 0.4 ml/min, and deltaSFP was 5.7 +/- 1.6 mmHg. Nitro-L-arginine infusion alone reduced RBF to 5.3 +/- 0.5 ml/min (P < 0.05); with nitroprusside infusion, RBF was restored to 8.3 +/- 0.7 ml/min. In this condition (NO clamp), deltaSFP was markedly increased to 19.6 +/- 3.2 mmHg (P < 0.05). By contrast, deltaSFP, which was virtually abolished during enalaprilat alone (0.2 +/- 0.3 mmHg), was not significantly different from controls during AngII clamp (8.2 +/- 1.0 mmHg). These data suggest that NO may well be released upon TGF activation. By contrast, AngII is not dynamically involved in TGF activation, but may modulate the TGF response. Thus, dynamic release of NO during TGF activation mitigates the TGF response, so that it will offset the action of a primary, as yet undefined, vasoconstrictor mediator. The source of this NO, macula densa or endothelium, remains to be elucidated.

scholarly journals Adenosine A2 receptors modulate tubuloglomerular feedback

2010 ◽  
Vol 299 (2) ◽  
pp. F412-F417 ◽  
Author(s):  
Mattias Carlström ◽  
Christopher S. Wilcox ◽  
William J. Welch
Keyword(s):  
Receptor Antagonist ◽  
Low Dose ◽  
Tubuloglomerular Feedback ◽  
High Dose ◽  
Sprague Dawley ◽  
Simultaneous Application ◽  
Sprague Dawley Rats ◽  
Flow Pressure ◽  
Stop Flow ◽  
A2 Receptors

Adenosine can mediate the tubuloglomerular (TGF) response via activation of A1 receptors on the afferent arteriole, but both adenosine A1 and A2 receptors can regulate preglomerular resistance. We tested the hypothesis that adenosine A2 receptors offset the effect of A1 receptors and modulate the TGF. Maximal TGF responses were measured in male Sprague-Dawley rats as changes in proximal stop-flow pressure (ΔPSF) in response to increased perfusion of the loop of Henle (0 to 40 nl/min) with artificial tubular fluid (ATF). The maximal TGF response was studied after 5 min of intratubular perfusion (10 nl/min) with ATF alone, or with ATF plus the A2A receptor antagonist (ZM-241385; 10−7 or 10−5 mol/l), A1 receptor antagonist (PSB-36; 10−8 mol/l), or with a combination of A1 (PSB-36; 10−8 mol/l) and A2A (ZM-241385; 10−7 mol/l) antagonists. The maximal TGF response (ΔPSF) with ATF alone was 11.7 ± 1.0 mmHg. Specific A2 inhibition (low dose) enhanced the maximal TGF response (15.7 ± 0.8 mmHg; P < 0.01), whereas a high dose (unspecific inhibition) attenuated the response (5.0 ± 0.4 mmHg; P < 0.001). A1 inhibition alone led to a paradoxical TGF response, with an increase in PSF of 3.1 ± 0.5 mmHg ( P < 0.05). Simultaneous application of A1 and A2 antagonists abolished the TGF response (ΔPSF: 0.4 ± 0.3 mmHg). In conclusion, adenosine A2 receptors modulate the TGF response by counteracting the effects of adenosine A1 receptors.

ANG II-induced downregulation of RBF after a prolonged reduction of renal perfusion pressure is due to pre- and postglomerular constriction

2004 ◽  
Vol 286 (5) ◽  
pp. R865-R873 ◽  
Author(s):  
Charlotte Mehlin Sorensen ◽  
Paul Peter Leyssac ◽  
Max Salomonsson ◽  
Ole Skott ◽  
Niels-Henrik Holstein-Rathlou
Keyword(s):  
Perfusion Pressure ◽  
Plasma Renin ◽  
Renal Perfusion ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Renal Perfusion Pressure ◽  
Sprague Dawley Rats ◽  
Proximal Tubular ◽  
Tubular Flow ◽  
Over Time

Previous experiments from our laboratory showed that longer-lasting reductions in renal perfusion pressure (RPP) are associated with a gradual decrease in renal blood flow (RBF) that can be abolished by clamping plasma ANG II concentration ([ANG II]). The aim of the present study was to investigate the mechanisms behind the RBF downregulation in halothane-anesthetized Sprague-Dawley rats during a 30-min reduction in RPP to 88 mmHg. During the 30 min of reduced RPP we also measured glomerular filtration rate (GFR), proximal tubular pressure (Pprox), and proximal tubular flow rate (QLP). Early distal tubular fluid conductivity was measured as an estimate of early distal [NaCl] ([NaCl]ED), and changes in plasma renin concentration (PRC) over time were measured. During 30 min of reduced RPP, RBF decreased gradually from 6.5 ± 0.3 to 6.0 ± 0.3 ml/min after 5 min (NS) to 5.2 ± 0.2 ml/min after 30 min ( P < 0.05). This decrease occurred in parallel with a gradual increase in PRC from 38.2 ± 11.0 × 10-5 to 87.1 ± 25.1 × 10-5 Goldblatt units (GU)/ml after 5 min ( P < 0.05) to 158.5 ± 42.9 × 10-5 GU/ml after 30 min ( P < 0.01). GFR, Pprox, and [NaCl]ED all decreased significantly after 5 min and remained low. Estimates of pre- and postglomerular resistances showed that the autoregulatory mechanisms initially dilated preglomerular vessels to maintain RBF and GFR. However, after 30 min of reduced RPP, both pre- and postglomerular resistance had increased. We conclude that the decrease in RBF over time is caused by increases in both pre- and postglomerular resistance due to rising plasma renin and ANG II concentrations.

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.

Acute arterial hypertension inhibits proximal tubular fluid reabsorption in normotensive rat but not in SHR

2004 ◽  
Vol 286 (4) ◽  
pp. R726-R733 ◽  
Author(s):  
Christopher Walstead ◽  
Kay-Pong Yip
Keyword(s):  
Arterial Hypertension ◽  
Sprague Dawley ◽  
Acute Hypertension ◽  
Continuous Increase ◽  
Spontaneously Hypertensive ◽  
Fluid Reabsorption ◽  
Sprague Dawley Rats ◽  
Proximal Tubular ◽  
Tubular Flow ◽  
Tubular Fluid Reabsorption

The effect of acute arterial hypertension on proximal tubular fluid reabsorption was investigated in Sprague-Dawley rats and spontaneously hypertensive rats (SHR) by measuring proximal tubular flow with a nonobstructive optical method. Under control conditions, spontaneous tubular flow was oscillating at 0.02-0.03 Hz in Sprague-Dawley rats. Acute hypertension induced an immediate increase of mean tubular flow (50% increase after 20 min of hypertension) and augmentation of oscillatory amplitude. Acute hypertension did not alter single-nephron blood flow as measured by laser-Doppler velocimetry ( n = 12), suggesting that the increase of tubular flow was due to inhibition of reabsorption but not increase of filtration. By contrast, spontaneous tubular flow was fluctuating aperiodically in SHR. Acute hypertension did not induce a continuous increase of tubular flow or an increase in amplitude of fluctuations ( n = 15). When apical Na+/H+ exchanger activity of proximal tubule was monitored, acute hypertension did not alter the activity in SHR ( n = 8), while similar procedures had been shown to inhibit apical Na+/H+ exchanger activity of proximal tubules by more than 40% in Sprague-Dawley rats. These observations suggest that acute hypertension inhibits proximal tubular fluid reabsorption by inhibiting apical Na+/H+ exchanger activity in Sprague-Dawley rats and that this mechanism is impaired in SHR.

scholarly journals Dynamic interaction between myogenic and TGF mechanisms in afferent arteriolar blood flow autoregulation

2000 ◽  
Vol 279 (5) ◽  
pp. F858-F865 ◽  
Author(s):  
Matthew Walker ◽  
Lisa M. Harrison-Bernard ◽  
Anthony K. Cook ◽  
L. Gabriel Navar
Keyword(s):  
Blood Flow ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Dynamic Activity ◽  
Analog To Digital ◽  
Sprague Dawley Rats ◽  
Response Slope ◽  
Tubular Flow ◽  
Collective Interactions

The dynamic activity of afferent arteriolar diameter (AAD) and blood flow (AABF) responses to a rapid step increase in renal arterial pressure (100–148 mmHg) was examined in the kidneys of normal Sprague-Dawley rats ( n = 11) before [tubuloglomerular feedback (TGF)-intact] and after interruption of distal tubular flow (TGF-independent). Utilizing the in vitro blood-perfused juxtamedullary nephron preparation, fluctuations in AAD and erythrocyte velocity were sampled by using analog-to-digital computerized conversion, video microscopy, image shearing, and fast-frame, slow-frame techniques. These assessments enabled dynamic characterization of the autonomous actions and collective interactions between the myogenic and TGF mechanisms at the level of the afferent arteriole. The TGF-intact and TGF-independent systems exhibited common initial (0–24 vs. 0–13 s, respectively) response slope kinetics (−0.53 vs. −0.47% ΔAAD/s; respectively) yet different maximum vasoconstrictive magnitude (−11.28 ± 0.1 vs. −7.02 ± 0.9% ΔAAD; P < 0.05, respectively). The initial AABF responses similarly exhibited similar kinetics but differing magnitudes. In contrast, during the sustained pressure input (13–97 s), the maximum vasoconstrictor magnitude (−7.02 ± 0.9% ΔAAD) and kinetics (−0.01% ΔAAD/s) of the TGF-independent system were markedly blunted whereas the TGF-intact system exhibited continued vasoconstriction with slower kinetics (−0.20% ΔAAD/s) until a steady-state plateau was reached (−25.9 ± 0.4% ΔAAD). Thus the TGF mechanism plays a role in both direct mediation of vasoconstriction and in modulation of the myogenic response.

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