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.

Effect of angiotensin II receptor blockade on proximal tubular fluid reabsorption

1997 ◽  
Vol 273 (2) ◽  
pp. R510-R517 ◽  
Author(s):  
P. P. Leyssac ◽  
F. M. Karlsen ◽  
N. H. Holstein-Rathlou
Keyword(s):  
Angiotensin Ii ◽  
Flow Rate ◽  
Feedback Mechanism ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Angiotensin Ii Receptor ◽  
Fluid Reabsorption ◽  
Nacl Concentration ◽  
Proximal Tubular ◽  
Tubular Fluid Reabsorption

The effect of physiological concentrations of angiotensin II on proximal tubular fluid reabsorption remains controversial. To investigate the effect of blockade of intratubular AT1 receptors on tubular reabsorption, losartan (10(-5) M) was administered by microperfusion into an early proximal convolution of halothane-anesthetized Sprague-Dawley rats. Four parameters that depend on the rate of proximal fluid reabsorption were measured: proximal intratubular pressure (Pprox), early and late proximal flow rate, and early distal NaCl concentration. Pprox decreased by 0.5 +/- 0.1 mmHg, late proximal flow rate decreased by 2.0 +/- 0.8 nl/min, and early distal NaCl concentration decreased by 4.3 +/- 0.8 mM (mean +/- SE). No changes were observed after microperfusion with saline. Because the tubuloglomerular feedback mechanism was operating in the closed-loop mode, the decreased NaCl load to the macula densa will be compensated by an increase in the single-nephron glomerular filtration rate. In agreement with this, the early proximal flow rate, measured proximal to the site of losartan administration, increased by 5.7 +/- 1.3 nl/min. The increase in the rate of proximal reabsorption between the early and late proximal convolutions was estimated to be 7.8 nl/min (approximately 36%). It is concluded that a decrease in local luminal angiotensin II levels and/or AT1 receptor activity under free flow conditions increases the rate of proximal tubular fluid reabsorption.

Failure of tubule fluid osmolarity to affect feedback regulation of glomerular filtration

1980 ◽  
Vol 239 (5) ◽  
pp. F427-F432 ◽  
Author(s):  
J. P. Briggs ◽  
J. Schnermann ◽  
F. S. Wright
Keyword(s):  
Flow Rate ◽  
Feedback Regulation ◽  
Solute Concentration ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Perfusion Flow ◽  
Sprague Dawley Rats ◽  
Nacl Concentration ◽  
Osmotic Agents ◽  
Feedback Responses

Experiments were performed in Sprague-Dawley rats in order to distinguish between sodium chloride and total solute concentration as possible luminal signals capable of eliciting tubuloglomerular feedback responses. Early proximal flow rate (VEP), an index of nephron filtration rate, was measured without perfusion of the loop of Henle and during retrograde perfusion with solutions containing 20, 35, 60 to 100 mM NaCl and varying amounts of either urea or mannitol to achieve total solute concentrations of 130, 280, or 400 mosM. Perfusion flow rate was kept constant at 20 nl/min. Perfusion with a solution containing 20 mM NaCl and made hypo-, iso-, or hypertonic with urea or mannitol caused little or no change in VEP. Perfusion with a 35 mM NaCl solution made hypo-, iso-, or hypertonic with mannitol resulted in a fall of VEP of 6-7 nl/min. When NaCl concentration was 60 mM, VEP fell by 10-14 nl/min with solutions made hypo-, iso-, or hypertonic with urea or mannitol. With 100 mM NaCl solutions made hypo-, iso-, or hypertonic with mannitol, VEP fell approximately 12 nl/min. These results indicate that feedback responses are determined by the NaCl concentration of the perfusate and that this NaCl dependency is not modified by varying perfusate osmolarity between 130 and 400 mosM with urea or mannitol as osmotic agents.

scholarly journals Tubuloglomerular feedback in Dahl rats

1998 ◽  
Vol 274 (6) ◽  
pp. R1561-R1569 ◽  
Author(s):  
Finn M. Karlsen ◽  
Paul P. Leyssac ◽  
Niels-Henrik Holstein-Rathlou
Keyword(s):  
Flow Rate ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Compensatory Response ◽  
High Salt Diet ◽  
Salt Diet ◽  
Sprague Dawley Rats ◽  
Intratubular Pressure ◽  
Low Salt ◽  
Experimental Rat Model

We have previously demonstrated a loss of autoregulation in Dahl salt-sensitive (Dahl-S) rats rendered hypertensive on a high-salt diet. To determine whether this was due to a decreased activity of either the myogenic or the tubuloglomerular feedback (TGF) response, we tested the TGF response in both Dahl-S and salt-resistant Dahl rats on high- and low-salt diets. TGF was investigated in the closed-loop mode with a videometric technique, in which the response in late proximal flow rate to perturbations in Henle flow rate was measured. All Dahl rats showed a similar compensatory response to perturbations around the natural operating point, with a TGF response that was more efficient than in normotensive Sprague-Dawley rats. No evidence of decreased TGF responsiveness in hypertensive Dahl-S rats was found. The results suggest that the loss of autoregulation in hypertensive Dahl-S rats is due to a compromised myogenic response. We also measured the free-flow proximal intratubular pressure in Dahl rats. Perfectly regular oscillations were demonstrated in all Dahl series, including the hypertensive Dahl-S rats. This is the first demonstration of regular oscillations in an experimental rat model of hypertension.

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.

Quantitative characterization of the tubuloglomerular feedback response: effect of growth

1984 ◽  
Vol 247 (5) ◽  
pp. F808-F815 ◽  
Author(s):  
J. P. Briggs ◽  
G. Schubert ◽  
J. Schnermann
Keyword(s):  
Flow Rate ◽  
Tubuloglomerular Feedback ◽  
Loop Of Henle ◽  
Sprague Dawley ◽  
Maximum Slope ◽  
Sprague Dawley Rats ◽  
Single Nephron ◽  
Renal Micropuncture ◽  
The Right

Studies were performed to characterize quantitatively the effect of changing loop of Henle flow rate on single nephron glomerular filtration rate (SNGFR) in male Sprague-Dawley rats of varying body weight. Rats weighing 100, 220, and 350 g were studied using standard renal micropuncture techniques. The relationship between loop of Henle flow rate (VLP) and SNGFR was characterized for individual nephrons by multiple determinations of SNGFR during loop perfusion. An inverse sigmoidal relationship was observed that could be described as delta SNGFR = a/(1 + ek(b-VLP], where delta SNGFR is the change in SNGFR from the value measured at zero loop flow, a is delta SNGFRmax, the maximum change, b is V1/2, the flow rate at which the response is half maximum, and k is [4f' (V1/2)]/a with f' (V1/2) the slope at V1/2. delta SNGFRmax increased with increasing body size (7.9 +/- 1.16, 18.9 +/- 0.90, and 25.2 +/- 2.73 nl/min, respectively, in the three groups), and the curve shifted to the right (V1/2 = 10.3 +/- 0.8, 15.4 +/- 0.83, and 22.3 +/- 1.22 nl/min). The maximum slope increased (f' (V1/2) = 0.9 +/- 0.19, 1.7 +/- 0.16, and 3.2 +/- 0.70), but the exponential constant k was uninfluenced by growth. Independent of rat size, a 10% increase in loop flow at the midpoint produced at 5-10% decrease in SNGFR. Free-flow values of SNGFR and VLP were found to lie in the most sensitive range of the feedback curve.

A dynamic model of the tubuloglomerular feedback mechanism

1990 ◽  
Vol 258 (5) ◽  
pp. F1448-F1459 ◽  
Author(s):  
N. H. Holstein-Rathlou ◽  
D. J. Marsh
Keyword(s):  
Dynamic Model ◽  
Stokes Equations ◽  
Dynamic Properties ◽  
Chloride Concentration ◽  
Feedback Mechanism ◽  
Macula Densa ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Nacl Concentration ◽  
Phase Relationships

We have reported oscillations in proximal tubular pressure and flow and in distal tubular pressure and chloride concentration in halothane-anesthetized Sprague-Dawley rats. These variables oscillated at the same frequency in each animal, approximately 35 mHz, but were out of phase with each other. We suggested that the oscillation arises within the tubuloglomerular feedback (TGF) system. As a test of this hypothesis, we have now developed a dynamic model to determine whether it can simulate the measured frequency and phase relationships with a realistic set of parameters. The model includes a detailed representation of pressure and flow in the tubules based on a reduced version of the Navier-Stokes equations. The NaCl concentration at the macula densa was used as the signal to the TGF mechanism. The tubular NaCl concentration was modeled by a partial differential equation based on conservation of mass. For a realistic set of parameter values the model accurately predicted oscillations with the same frequency and phase relationships among the oscillating variables as was found experimentally. Moreover, tubular NaCl handling significantly influenced the dynamic properties of the TGF system. Thus the model predicted a substantial phase shift of the NaCl concentration relative to the flow oscillation at the macula densa. The results are consistent with the hypothesis that the oscillations are caused by the TGF mechanism. The results further support the notion that the delays and damping caused by the tubule are responsible for the limited high-frequency response of renal autoregulation.

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.

Ameliorating effects of cloperastine on dysfunction of the urinary bladder caused by cerebral infarction in conscious rats

2009 ◽  
Vol 87 (11) ◽  
pp. 893-899 ◽  
Author(s):  
Gen Yamamoto ◽  
Fumio Soeda ◽  
Tetsuya Shirasaki ◽  
Kazuo Takahama
Keyword(s):  
Urinary Bladder ◽  
Cerebral Infarction ◽  
Flow Rate ◽  
Bladder Capacity ◽  
Left Middle Cerebral Artery ◽  
Sprague Dawley ◽  
Urinary Bladder Dysfunction ◽  
Sprague Dawley Rats ◽  
Urethral Resistance ◽  
Effective Doses

We investigated the effects of the centrally acting antitussives dextromethorphan and cloperastine on urinary bladder dysfunction 24 h after cerebral infarction in rats using the cystometry technique. First, cystometrography was performed in conscious male Sprague–Dawley rats. Cerebral infarction was then induced by occlusion of the left middle cerebral artery. Twenty-four hours after cerebral infarction, the effect of each drug on micturition disorder was estimated for 5 parameters: bladder capacity, maximum voiding pressure, micturition latency, flow rate, and urethral resistance. Cerebral infarction markedly reduced bladder capacity, micturition latency, and flow rate and increased urethral resistance. After cerebral infarction, intravenous dosing of saline had no effect on these parameters. Dextromethorphan (20 mg/kg) and cloperastine (2.5 and 5.0 mg/kg) at antitussive effective doses significantly increased bladder capacity and micturition latency. Unlike dextromethorphan, cloperastine ameliorated decreases in flow rate and increases in urethral resistance caused by cerebral infarction. These results suggest that cloperastine may have therapeutic value for the treatment of disorders of the micturition reflex associated with cerebral infarction, and that the drug may become a base compound from which to develop more active drugs for such disorders.

Abstract 20074: Hemodynamic Profile of Prolonged Normothermic, Mild Hypothermic, and Deep Hypothermic Emergency Cardiopulmonary Bypass Reperfusion in Rats

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Ingrid A Magnet ◽  
Florian Ettl ◽  
Andreas Schober ◽  
Alexandra-Maria Warenits ◽  
Christoph Testori ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Flow Rate ◽  
Mild Hypothermia ◽  
Temperature Profiles ◽  
Sprague Dawley ◽  
Flow Rates ◽  
Circulating Water ◽  
Sprague Dawley Rats ◽  
Hemodynamic Profile ◽  
75Th Quartile

Background: The hemodynamic profile of rats randomized into prolonged normothermic (NT, 37±0.5°C), mild hypothermic (MH, 33±0.5°C) or deep hypothermic (DH, 27±0.5°C) reperfusion with emergency cardiopulmonary bypass (ECPB), following refractory ventricular fibrillation cardiac arrest (VF CA) was explored. Methods: Fifty adult male Sprague-Dawley rats were put on bypass for 15 min, following 10 min of VF CA. The ECPB setup included a circulating water bath which temperature controlled all animals at target. After 15 min, rats were defibrillated, weaned from bypass, and controlled at 33°C (MH, DH) or 37°C (NT) externally. All rats received a single dose of epinephrine (30 μg/kg), heparin and sodium bicarbonate with the crystalloid priming of the ECPB circuit. ECPB flow rate was kept at 100 mL/kg in all groups. Mean arterial pressure (MAP) was continuously monitored in the femoral artery and is presented as median with 25th/75th quartile mmHg. Results: See figure. There was no difference in MAP before or during CA. For the first 5 min of resuscitation, MAP at a given ECPB flow rate was highest in the DH group (DH 84(69;89), MH 51(49;61), NT 48(37;55) , p = <.001). This was reversed during the last 5 min on bypass (DH 35(30;42), MH 44(37;64), NT 42(33;67), p = .034). For 10 min off bypass, the DH group was relatively hypotensive (DH 46(40;62, MH 64(60;77), NT 61(54;77), p = .005), which was again reversed for the remaining post resuscitation period (DH 68(60;78), MH 59(54;66), NT 53(49;62), p = .008). Conclusions: While the temperature profiles of NT and MH reperfusion were similar, DH caused initially higher pressures followed by a period of hypotension as compared to NT and MH groups at identical epinephrine doses and ECPB flow rates. Off bypass, DH animals were again relatively hypotensive, coinciding with their rewarming to mild hypothermia. Further experiments are needed to determine the cause of this, like hypothermic vasoconstriction, or altered pharmacokinetics.

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