Micropuncture studies on the dog kidney

Summary Micropuncture studies have been carried out on the dog kidney in order to evaluate the proximal tubular response in different experimental settings. When total and single nephron GFR varied spontaneously, a constancy of fractional reabsorption was observed. When GFR was drastically reduced following regitine-induced hypotension no significant difference in late proximal fractional reabsorption was noted when compared to controls, but lateral water flux and reabsorptive capacity fell markedly. Finally, during ethacrynic acid administration late proximal TF/P inulin remained constant, transit time was prolonged, and tubular radius and intratubular pressure increased. The lateral water flux was slightly reduced and reabsorptive capacity showed a moderate decrease.These studies have provided normal values for the reabsorptive characteristics of the canine proximal tubule (radius, transit time, intratubular pressure, lateral water flux, and reabsorptive capacity) and indicate that, under control conditions and during hypotension and diuretic administration, the dog and the rat have similar proximal tubular responses.Supported by a Medical Research Fellowship of the Medical Research Council of Canada.     

Micropuncture studies on the filtration rate of single superficial and juxtamedullary glomeruli in the rat kidney

Summary Single nephron filtration rates of superficial and juxtamedullary nephrons were determined in high and low sodium rats. Single nephron GFR was calculated from TF/P inulin and tubular flow rate in superficial nephrons and single juxtamedullary GFR from corresponding data in long loops of Henle. In low sodium rats superficial nephron GFR was 23.5±6.4 (SD)×10^–6 ml/min×g KW, juxtamedullary nephron GFR was 58.2±13.6 and total kidney GFR (C _In) was 0.94±0.16 ml/min×g KW. Using these single nephron values, total kidney GFR and a total number of 30,000 glomeruli per kidney, the number of superficial and juxtamedullary glomeruli was calculated to be 23,267 and 6,733, respectively. During high sodium diet superficial nephron GFR increased to 38.1±11.3 and single juxtamedullary GFR decreased to 16.5±6.6, total kidney GFR increasing to 1.01±0.24. Calculation again revealed the same distribution of the two nephron types. End-proximal TF/P inulin in superficial nephrons was 2.36±0.36 in low sodium and 2.31±0.28 in high sodium rats. Loops of Henle TF/P inulin and intratubular flow rate were inversely related: the highest TF/P inulin values and lowest intratubular flow rates were found in the descending limb. These data quantify the distribution of superficial and juxtamedullary nephrons on a functional basis and suggest a mechanism by which the kidney adjusts sodium excretion by altering the contribution of each nephron type to total kidney GFR.Supported by the Deutsche Forschungsgemeinschaft and the U.S. Department of the Army, through its European Research Office.     

Function of juxtamedullary nephrons in normotensive and chronically hypertensive rats

Summary The function of juxtamedullary nephrons was investigated by micropuncture of long loops of Henle at the exposed papilla in normal rats and in the untouched kidney of rats with experimental hypertension (unilateral Goldblattclip). With increasing blood pressure (range from 90–190 mm Hg) a continuous rise in juxtamedullary single nephron glomerular filtration rate was observed. Juxtamedullary single nephron GFR averaged 60×10^–6 ml/min/g K.W. in the control group (mean arterial blood pressure 116 mm Hg) and 114×10^–6 ml/min/g K.W. in the hypertensive group (mean arterial blood pressure (164 mm Hg). There was no change in superficial single nephron GFR (30×10^–6 ml/min/g K.W.) but a slight increase in total kidney GFR from 1.07 to 1.28 ml/min g K.W. In both the normotensive and the hypertensive animals, tubular fluid-to-plasma (TF/P) inulin ratio and intratubular flow rate in the descending limb of the long loops of Henle were not statistically different from those found in the ascending limb. Intratubular flow rate in the hypertensive rats was twice as high as in the controls; the mean TF/P inulin ratios in the two groups did not differ from each other. Appearance time of lissamine green in the long loops of Henle and in the collecting ducts was shortened in the hypertensive animals. It is concluded that there is no autoregulation of glomerular filtration rate in juxtamedullary nephrons. The increased juxtamedullary GFR may contribute to the elevated urinary excretion of the unclipped kidney in hypertensive rats.This paper was presented before the German Physiological Society, Mainz, March 1969 [11].     

Autoregulation of superficial nephron function in the alloperfused dog kidney

Isolated dog kidneys were each pumpperfused by another dog during 4 experimental periods at perfusion pressures (PP) of 21, 17, 13, and 8 kPa, resp. (i. e. 160, 130, 95, and 60 mm Hg). At the 3 highest PP values, the total kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were perfectly autoregulated while at the lowest value both values were significantly lowered. No significant difference was observed between the single nephron GFR (SNGFR) of periods 1 and 2; in period 3 (PP=13 kPa) a lower value was observed (P<0.05). Free flow pressure in proximal convolution (FFP), stop-flow pressure (SFP), and peritubular capillary pressure (PCP) were not different in period 2 than in period 1, but were significantly lower in period 3 (P=0.02–0.05). Effective filatration pressure (EFP) was the highest in period 1, decreasing significantly with decreasing PP. Filtration pressure equilibrium was observed in period 4 at PP 8 kPa. Total blood flow resistance (R_T) fell with decreasing PP, the drop being due to a steep decline in afferent resistance (R_A). Efferent resistance (R_E) increased as PP decreased. Ultrafiltration coefficient (K_f) rose with declining PP both within and outside the autoregulatory range. The results indicate that the lower limit of autoregulation is higher in superficial nephrons than in the whole kidney.     

Balance between tubular flow rate and net fluid reabsorption in the proximal convolution of the rat kidney

Summary In rats with hereditary Diabetes insipidus (Brattleboro strain) proximal fluid reabsorption was studied during spontaneous variations of GFR. Independent of kidney weight and arterial blood pressure total kidney GFR varied between 0.35 ml/min×gKW and 1.8 ml/min×gKW, while single nephron filtrate showed a variation between 18 nl/min×gKW and 66 nl/min×gKW. End-proximal TF/P inulin of 78 fluid samples did not correlate with filtration rate and averaged 2.38±0.55 S.D. Also, proximal transit time was independent of filtration rate with a mean of 9.7 sec±1.1 S.D. These results imply a direct correlation between mean luminal radius and filtration rate, which was demonstrated by microphotography of the renal surface.Our data show that complete glomerulo-tubular balance in the proximal tubule exists during spontaneous variations of glomerular filtration rate. In support of the hypothesis ofGertz [4,6] the lateral net fluid flux was found to be linearly dependent upon tubular surface area. In addition, intratubular volume changed in direct proportion to single nephron filtrate. The present results are interpreted to further strengthen the assumption of a critical influence of tubular geometry on proximal fluid reabsorption during spontaneous variations of GFR.Supported by the Deutsche Forschungsgemeinschaft and the U.S. Department of the Army, through its European Research Office.     

Tubuloglomerular feedback and autoregulation of glomerular filtration rate in Wistar-Kyoto spontaneously hypertensive rats

Experiments were done in Wistar-Kyoto spontaneously hypertensive rats (SHR) to examine the efficiency of autoregulatory adjustments of kidney and nephron filtration rate (GFR) to acute changes in blood pressure (BP) over a broad blood pressure range. When BP of the SHR was reduced from 158±7 to 118 ±3 mm Hg by aortic clamping, kidney-GFR remained unchanged from 1.19±0.11 to 1.17±013 ml·min^–1·g^–1 kidney weight (KW), respectively. Single nephron GFR (SNGFR) measured at early distal tubule sites was similarly unchanged with the same BP change, 27.9±1.5 vs. 24.9±2.1 nl·min^–1·g^–1 KW (P>0.10). Proximal and distal estimates of SNGFR were significantly different from each other at high BP (7 nl·min^–1·g^–1,P<0.025), but were not different at low BP (2.0 nl·ml^–1·g^–1,P>0.10). Studies assessing tubuloglomerular feedback activity were done with orthograde perfusion of the loop of Henle using recollections of early proximal flow rate (EPFR) as an index of change of glomerular filtration rate. A change in perfusion rate from 0 to 45 nl·min^–1 induced a reduction in early proximal flow rate of 40.5 ±4.5%. Juxtaglomerular renin activity of superficial nephrons was 36.2±4.3 in the SHR, a value insignificantly different from 23.7±4.4 ng Angiotensin II amide·0.1 ml^–1·h^–1. 5 glomeruli^–1 in normal controls (P>0.05). The SHR appears to behave as a normal animal with respect to tubologlomerular feedback and autoregulatory renal vascular adjustments. Like normal rat models, the SHR demonstrated dependence on maintenance of distal filtrate delivery to achieve single nephron GFR autoregulation.Financial support for these studies and for Dr. Ploth were made available by funds from the Deutsche Forschungsgemeinschaft     

Filtration in surface glomeruli as regulated by flow rate through the loop of henle

Summary A new pressure transducer microperfusion system has been used to measure quantitatively SN GFR, early proximal free flow pressure and stop flow pressure of varying flow rates through the loop of Henle in the range of 0 to 50 nl/min. Perfusing the loop with an isoosmolal artificial tubular fluid at physiological flow rates SN GFR was 19.9±1.1 and 27.7±1.0 nl/min in two different strains of antidiuretic rats. SN GFR increased when loop perfusion was interrupted. The question whether a feedback control mechanism of SN GFR is operative in the rat kidney was evaluated in further experiments in which early proximal tubular pressure was measured in functionally isolated proximal convolutions in vivo under conditions of constant flow as well as stopped flow. Experiments in which perfusion rate through the loop of Henle was varied demonstrated the existence of a feedback signal which originates downstream of the late proximal convolution and which affects filtration into individual early proximal segments. This feedback mechanism exhibited an asymmetrical behaviour: Elevation of loop perfusion above the control value resulted in an early proximal pressure drop, under simulated free flow conditions as well as under stop flow conditions. In contrast lowering of perfusion rate below the predetermined physiological value had no significant effect on early proximal pressures.Index of Abbreviations FFP free flow pressure - P _a blood pressure - P _G mean glomerular capillary pressure - PCT proximal convoluted tubule - P _tub intratubular hydrostatic pressure - SFP stop flow pressure - SN GFR single nephron glomerular filtration rate - TF tubular fluid - TF/P concentration ratio between tubular fluid and plasma - V_(TF) collected volume of tubular fluid, flow rate Supported by Deutsche ForschungsgemeinschaftParts of the present work have been presented at the following meetings: Int. Symp. on Renal Handling of Sodium, Brestenberg1971; Workshop of Renal Micropuncture Techniques, Yale University 1971; Int. Congress of Nephrology, Mexico City 1972.     

The effects of chronic papillary necrosis on acid excretion

Complete papillary necrosis in rats can be induced within 1 month following a single injection of 2-bromoethylamine hydrobromide (BEA) (50 mg, i.v.). Utilizing a combination of clearance and balance techniques the effects of complete absence of the papilla was examined as regards urinary acidification, whole kidney glomerular filtration rate (GFR), single nephron GFR, and morphology. Whole kidney GFR was not different from control, however, the percent filtering juxtamedullary nephrons was markedly diminished (87.2±2.1 vs. 31.5±3.6% filtering, control vs. BEA, respectively,P<0.001) and significantly reduced in the superficial nephrons (80.6±3.6 vs. 62.2±6.1% filtering, control vs. BEA, respectively,P<0.05). There was a significant decrease in juxtamedullary single nephron GFR and an increase in the superficial single nephron GFR as assessed by the quantitative Hanssen's technique in the animals with chronic papillary necrosis. Complete papillary necrosis was associated with normal arterial bicarbonate concentration, pH, and plasma electrolyte concentrations. At the same degree of acidemia (induced by NH₄Cl administration) minimal urinary pH, ammonium excretion, and titratable acid excretion were not different than seen in age matched controls. The response to Na₂SO₄ infusion and phosphate infusion was the same in both groups of animals. The urineblood (U-B)pCO₂, an index of urinary acidification, was identical in BEA and control animals. Scanning electron microscopy showed scarring of the juxtamedullary glomeruli one month after BEA. The papilla was sloughed and lying free in the renal pelvis in every experimental animal. These data demonstrate that complete papillary necrosis is not associated with acidosis nor a defect in urinary acidification.     

The effect of saline infusion and hemorrhage on glomerular filtration pressure and single nephron filtration rate

Summary Single nephron filtration rate (GFRs) and effective glomerular filtration pressure (EFP) measured as the difference between intratubular stop-flow (SFP) and free-flow pressures (FFP), were determined in control rats and following saline infusion or hemorrhage. Infusion of isotonic or 4% NaCl increased EFP and GFRs without significantly affecting TF/P inulin. These findings could not be related to changes in arterial blood pressure. Controlled bleeding produced a marked decrease in EFP and in GFRs, again without significant change in TF/P-inulin. In both infusion and hemorrhage the change in GFRs was disproportionately greater than the change in EFP. Analysis of the components of the filtration process suggests that elevation of EFP is attended by an increase in permeability of the filtering membrane. This sensitive dependence of GFRs upon EFP, combined with a demonstrated constancy of total kidney GFR (GFR_T) over a wide range of urine concentrations and flow rates, connotes a close regulation of EFP in this experimental animal.Supported by Deutsche Forschungsgemeinschaft.     

Renal autoregulation of blood flow and filtration rate in the rabbit

Electromagnetic flow techniques and inulin clearance were used to determine the autoregulatory capabilities of the rabbit kidney in vivo. Renal blood flow was measured in 13 animals over a renal perfusion pressure range of 40-110 mmHg. Normal renal blood flow averaged 3.2 +/- 0.3 ml.min-1.g kidney-1 and was efficiently autoregulated above a renal artery pressure of 75 mmHg. For every 10 mmHg renal pressure change above 75 mmHg renal blood flow changed only 0.96%. Renal perfusion pressure was reduced from 102 +/- 3 to 74 +/- 2 mmHg in six animals. Over this pressure range glomerular filtration rate was not significantly decreased and averaged 4.2 +/- 0.5 ml/min at high pressure compared to 4.0 +/- 0.5 ml/min at low perfusion pressure. Results show that the rabbit kidney autoregulates renal blood flow and glomerular filtration rate efficiently above 75 mmHg. This range of autoregulation compares well with the autoregulatory range of the dog. The results also show that in the autoregulatory range the rabbit and the rat appear to autoregulate with equal efficiency but that the rabbit kidney begins to autoregulate at a low perfusion pressure than the average of approximately 100 mmHg usually found in the rat.     

Number of nephrons in hypertrophic kidneys after unilateral nephrectomy in young and adult rats

Summary The number of functional nephrons in hypertrophied kidneys was determined in adult non diuretic rats which had been uni-nephrectomized either before 45 days (NY) or after 90 days (NO). This number was calculated by dividing the whole kidney GFR by the single nephron GFR, measured either by micropuncture or the¹⁴C-ferrocyanide infusion technique. Kidney weight was greater in NY rats (1.48±0.08 g SE) than in NO rats (1.23±0.10). In micropuncture experiments on NO rats the number of nephrones (34300±1600) was similar to that of normal adult rats. In NY rats this number was significantly greater (44100±1800,P<0.001).The ferrocyanide technique gave similar results (NO rats: 34800±2100; NY rats: 43900±3600) and indicated that the ratio of superficial to juxtamedullary SNGFR was not altered in the hypertrophied kidneys.The length of microdissected proximal tubules was increased in hypertrophied kidneys of both NY and NO rats and this increase affected thepars recta andpars convoluta equally.Single nephron GFR and F/P Inulin in late proximal and early distal tubules were similar in NO and NY rats.In conclusion, our results demonstrate that when uni-nephrectomy is performed on young rats, the compensatory hypertrophy of the remaining kidney is the result of an increase in both the size and the number of nephrons.     

The influence of sampling technique on the micropuncture determination of GFR and reabsorptive characteristics of single rat proximal tubules

Summary Studies have been carried out in order to assess the validity of the determination of the single nephron filtration rate by micropuncture techniques. By means of a double microscope and two investigators operating simultaneoulsy, intratubular pressure and single nephron transit time were recorded during sampling. The data indicate that collection of tubular fluid by means of aspiration significantly accelerates transit time, decreases intratubular pressure, and results in an increase of single nephron filtration rate. In contrast, spontaneously flowing collections were associated with insignificant alterations of transit time and intratubular pressure. Technical details underlying these observations have to some extent been delineated. The importance of these data with respect to artifactual alterations of single nephron parameters is discussed.Supported by a Medical Research Fellowship of the Medical Research Council fo Canada.     

Micropuncture studies after temporary ischemia of rat kidneys

Summary Micropuncture experiments were carried out on rat kidneys subjected to temporary ischemia (TI). Unilateral TI was performed by clamping the blood supply to the left kidney for 60 min. Time period between TI and investigating the kidney ranged from 1 h to 13 days. In another series of experiments blood supply to the left kidney was severely diminished for 24 h by a clip.-39% of animals developed anuria of the experimental kidney; in the other animals, urine flow rate was markedly decreased after TI (P<0.02). Employing the tracer microinjection technique considerable amounts (51%-oliguric kidneys; 17%-nonoliguric kidneys) of¹⁴C-labelled inulin injected into a proximal tubule of the damaged kidney were found in the urine of the contralateral kidney indicating backdiffusion of inulin through the damaged tubular epithelium. The amount of inulin recovered from both kidneys was decreased. Backdiffusion of inulin was detectable up to seven days after TI. Under control conditions 2% of inulin injected was found on the contralateral side, inulin recovered from both kidneys being approx. 100%. Dye intensity of Lissamine-green passing through the nephron was decreased noticeably after TI. Proximal tubular diameter and proximal free-flow pressure showed a large variability, the means being not significantly differnt from controls.—The results indicate that the concurrence of at least two factors are involved in the pathogenesis of acute renal damage induced by TI: Backdiffusion of tubular fluid through the damaged tubular epithelium and a decrease of glomerular filtration rate. The measurement of the clearance of inulin in kidneys damaged by ischemia does not represent the actual GFR, but underestimates this value proportionately to the degree of backdiffusion of inulin.Supported by the Deutsche Forschungsgemeinschaft, SFB 90, CARVAS.     

The effect of a converting enzyme inhibitor on autoregulation and intrarenal distribution of glomerular filtration in the rat

The role of the renin-angiotensin system in the autoregulation and distribution of the single nephron glomerular filtration rate (SNGFR) in anaesthetized, normotensive rats was investigated. SNGFR in outer cortical (OC) and inner cortical (IC) nephrons of the left kidney were measured with a modified Hanssen technique at three levels of renal arterial pressure (RAP): at a spontaneous arterial pressure; at a value within the autoregulatory limit, 100 mmHg; and at the lower limit of the autoregulatory range, 70 mmHg. This was done in control rats and in rats given a continuous i.v. infusion of the converting enzyme inhibitor (CEI) captopril (3 mg . h-1 X kg-1 BW). In control rats there was complete autoregulation of SNGFR in both OC and IC nephrons when RAP was reduced to 100 mmHg. Further reduction to 70 mmHg elicited different responses among the cortical layers, associated with a decrease in SNGFR. A fractional redistribution of glomerular filtration rate towards IC nephrons was evident. Administration of CEI at spontaneous RAP increased SNGFR in IC nephrons compared with values in control rats, but did not notably alter SNGFR in OC nephrons. Reduction of RAP to 100 mmHg during CEI infusion caused SNGFR to decrease below control values in both OC and IC nephrons, and the autoregulation as found in control rats was impaired. When RAP was lowered to 70 mmHg during CEI administration there was a progressive decrease in SNGFR in all cortical layers, although absolute changes were much greater in IC nephrons than in OC nephrons.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal and nephron hemodynamics in spontaneously hypertensive rats.

Renal and nephron hemodynamics were compared between anesthetized, nondiuretic, spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Although the mean arterial pressure was higher in SHR than in WKY, 158 VS. 114 mmHg, glomerular filtration rate (GFR) and renal blood flow (RBF) were similar in both groups. So were intrarenal hydrostatic pressures, single nephron GFR (SNGFR), and single nephron blood flow (SNBF). Accordingly, the increased renal vascular resistance (RVR) in SHR was due to predominant preglomerular vasoconstriction. In a second group of SHR, SHR-AC, the femoral arterial pressure was reduced acutely to 114 mmHg by means of aortic constriction above the renal arteries. The mean values for GFR, RBF, SNGFR, SNBF, and intrarenal hydrostatic pressures resembled those in SHR, whereas RVR was less in SHR-AC. These autoregulatory adjustments of RVR were again largely limited to the preglomerular vasculature. Efferent arteriolar resistance was similar in all three groups. We conclude that the enhanced RVR in 12-wk-old SHR is primarily a consequence of a physiological, autoregulatory response of afferent arteriolar resistance to the elevated arterial pressure. Further, RVR in SHR is not fixed and constant but responds appropriately to reductions in renal perfusion pressure.     

Influence of water-diuresis or saline volume expansion on deep nephron tubuloglomerular feedback

We have recently demonstrated the existence of a tubuloglomerular feedback mechanism in juxtamedullary nephrons in rat kidneys during antidiuresis. In the present experiments, we have investigated the influence of water-diuresis on Munich Wistar rats and in homozygote Brattleboro rats. We have also observed the effect of saline volume expansion on the tubuloglomerular feedback of juxtamedullary nephrons in Munich Wistar rats. For comparison, the feedback mechanism was also studied in surface nephrons during water-diuresis in Munich Wistar rats. Measurements of flow rate in the descending limb of Henle and single nephron glomerular filtration rate (GFR) using micropuncture at the renal papilla were performed, while the ascending limb was microperfused at varying perfusion rates with a modified Ringer solution. In surface nephrons early proximal flow rate, single nephron GFR and stop-flow pressure was measured during microperfusion of the end-proximal loop. No significant changes were measured in surface nephrons during water-diuresis: the tubular flow rates, feedback responses, stop-flow pressure and stop-flow pressure changes were similar to those during anti-diuresis. In juxtamedullary nephrons, Henle loop flow rate increases during water-diuresis but the feedback-mediated flow and single nephron GFR response curves obtained during microperfusion were unaltered compared to controls. Together, these results indicate that the feedback could be more activated during water-diuresis than during control conditions. On the other hand, during saline volume expansion, reduced tubuloglomerular feedback sensitivity was found as shown earlier for surface nephrons. The reduction of tubuloglomerular feedback sensitivity therefore seems to be important in maintaining salt-, but not water-balance.     

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

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.     

Intrarenal Distribution of Blood Flow and Glomerular Filtration during Chronic Unilateral Ureteral Obstruction

Paired hydronephrotic (HN) and hypertrophic (HT) rat kidneys were studied after 6 days with complete unilateral ureteral obstruction without exposing the kidneys. Total HN renal blood flow (RBF), estimated by total microsphere (MS) uptake and from local ¹²⁵I-antipyrine (Ap) uptake, averaged about 3/sec (n=147) for the extensor digitorum communis muscle and 3.39±0.68 m/sec (n=142) for the femoral quadriceps muscle. 4 of control. HN kidney GFR was reduced to about 1/2 of control level as estimated from inulin clearance of HT kidney times the HN to HT ratio for mean single nephron filtration rate, determined by ¹⁴C-ferrocyanide. Whereas blood flow (Ap) was proportionately reduced in outer and inner cortex (OC and 1C), fractional flow to the outer medulla (OM) was doubled as compared to controls (p < 0.01). Filtration was well preserved in deep as compared to superficial glomeruli with a smaller deep nonfiltering fraction (p > 0.02). Thus the results oppose the current concept that HN is characterized by disproportionate circulatory damage to IC and OM with little or no filtration in deep nephrons. In HT kidneys average RBF (MS) and GFR rose by about 1/2. Whereas total blood flow (Ap) rose proportionately in OC and IC, it remained at control level in OM, indicating dissociation between the total RBF and GFR and the effective blood flow to the OM zone.     

Evidence for feedback mediated reduction of glomerular filtration rate during infusion of acetazolamide

Systemic administration of acetazolamide (ACZ) causes glomerular filtration rate (GFR) to fall. Clearance and micropuncture experiments were done to define the mechanism of this drug effect. When rats were infused with ACZ intravenously, kidney GFR fell by 30% and single nephron (SN) GFR (measured by collecting distal tubule fluid) fell by 23%. Changes in arterial blood pressure, arterial pH, extracellular fluid volume, and proximal tubule pressure were not sufficient to account for the decrease in GFR. When SNGFR was measured by collecting proximal tubule fluid, with the loop of Henle having been blocked for 2–5 min, SNGFR was higher than the distally measured value and was not different than control. The results are consistent with the fall in GFR being caused by activation of the tubulo-glomerular feedback mechanism.