Anatomical and functional heterogeneity of nephrons in the rabbit: Microdissection studies and SNGFR measurements

Summary The single nephron glomerular filtration rate (SNGFR) was determined in superficial (S) and juxtamedullary (JM) nephrons of 10 anesthetized rabbits by the¹⁴C ferrocyanide infusion technique. The length of the proximal tubules and the volume of the glomeruli were also determined for the same nephrons. SNGFR was higher in JM than in S: 28.6±3.4 versus 22.6±3.0 nl/min,P<0.001. In JM nephrons, glomeruli were larger than in S: 1.3±0.1 versus 0.9±0.1 nl,P<0.001, whereas there was no difference between proximal tubule length in either category (S, 8.7±0.3 and JM, 8.9±0.5 mm). In 6 out of 8 animals, SNGFR was significantly correlated to glomerular volume. Lack of correlation was observed between SNGFR and length of proximal tubule in all animals but one. These results show that the rabbit, as well as small rodents and the dog, has a higher SNGFR in juxtamedullary than superficial glomeruli. Although this functional difference is not related to the length of the proximal tubule in each individual animal, the ratio between the mean SNGFR value and the mean length of the proximal tubule in superficial rabbit nephrons is similar to the ratio found in other species.     

The existence of a tubulo-glomerular feedback mechanism in the Amphiuma nephron

A single nephron tubulo-glomerular feedback control of the glomerular filtration rate, which is known in mammlian animals, could be one way by which amphibians regulate the glomerular filtration rate (GFR). To investigate whether theAmphiuma means shows any sign of a tubuloglomerular feedback control, micropuncture experiments were carried out. Six different series of experiments were performed.In the first series, tubular stop-flow pressure (SFP) was measured during distal tubular perfusion with amphibian Ringer solution at a rate of 10, 25 and 50 nl/min. A significant decrease of SFP was found at the three perfusion rates compared to the controls. In the second group, single nephron glomerular filtration rate (SNGFR) was measured, while the distal tubule was perfused at 10, 25 and 50 nl/min. At a perfusion rate of 10 nl/min the SNGFR did not decrease, whereas at 25 and 50 nl/min it decreased significantly. In the third group the perfusion pipette was located in the proximal tubule and the nephron was perfused at 10, 25 and 50 nl/min, while at the same time the proximal tubular stop-flow pressure was measured. No reduction of SFP was found at a perfusion rate of 10 nl/min, while significant reductions were noted at rates of 25 and 50 nl/min. In the fourth group the SNGFR was measured in the distal tubule beyond the macula densa and in Bowman's space of the same nephron. No significant difference was found. In the fifth group, the glomerular capillary pressure (GCP) was measured before and after blockade of the tubular fluid flow. No significant difference was found between these two measurements.The sixth series deals with the changes occuring at the single nephron level by the tubulo-glomerular feedback control. The single nephron filtration fraction (FF) was determined from efferent arteriolar protein concentration with and without a feedback-induced reduction of the SNGFR. The FF values were not significantly different from one another. From these results and data from the other series, the afferent (R _aff) and efferent (R _eff) arteriolar resistances were calculated.R _eff did not change, whileR _aff increased significantly when a feedback stimulus was applied.These experiments indicate the existence of a tubuloglomerular feedback control which depresses the SNGFR and SFP by contracting the afferent arteriole.     

Adaptive changes of juxtamedullary glomerular filtration in the remnant kidney

The participation of surviving juxtamedullary nephrons in the adaptive changes of glomerular filtration that occur in response to loss of functioning nephron mass was examined by direct micropuncture of the rat renal papilla. The solitary remnant kidney (RK) in rats with an 85% reduction of renal mass demonstrated strikingly elevated values for single nephron glomerular filtration rate (SNGFR) in both superficial (46.1±3.2 nl/min) and juxtamedullary (73.5±6.1 nl/min) nephrons in comparison to respective values observed in normal hydrophenic rats (superficial SNGFR=15.0±1.9nl/min,P<0.001, and juxtamedullary SNGFR=30.2±3.2 nl/min,P<0.001). In RK rats, the proximal portions of both superficial and juxtamedullary nephrons exhibited a marked increase in absolute fluid reabsorption as well as a markedly enhanced delivery of fluid to more distal portions of the nephron. These observations indicate that similar, not preferential, functional adaptations in glomerular filtration occur concommitantly in both superficial and juxtamedullary nephrons consequent to reduction of renal mass.     

Heterogeniety in regulation of glomerular function

The aim was to study differences in filtration driving forces and glomerular filtration rates between superficial and deep nephrons when urine flow rate was altered at the macula densa region. In young rats stop-flow pressures and single nephron glomerular filtration rates (SNGFR) were measured in the superficial proximal tubules and in the loops of Henle in the papilla. SNGFR was also measured with a modified Hanssen technique. The stop-flow pressures of superficial nephrons amounted to 30.9±0.8 mmHg (mean ± SE) and those of juxtamedullary nephrons to 52.2±1.6 mmHg. In the stop-flow condition the net driving filtration forces were calculated to be about 19 mmHg and 50 mmHg for the superficial and deep glomeruli, respectively. In free flow conditions both net driving forces were calculated to be 19 mmHg. The micropuncture technique gave a SNGFR value for superficial nephrons of 29.6±2.9 and for deep nephrons of 84.1±8.5 nl±min^-1 g^-1 kidney weight (KW). With a modified Hanssen technique the corresponding values were 25.8±3.3 and 27.7±2.9 nl. min^-1.g^-1KW. The tubuloglomerular feedback mechanism is considered to have a powerful regulatory influence on the glomerular filtration rate of deep nephrons.     

Studies on the mechanism of reduction in glomerular filtration rate after benzolamide

In previous studies, we have shown that benzolamide, a carbonic anhydrase inhibitor with diuretic activity confined primarily to the proximal tubule, causes a significant reduction in nephron filtration rate by increasing afferent and efferent arteriolar vascular resistance [30], possibly through an activation of tubuloglomerular feedback mechanism. The present studies were designed to determine if infusion of 1-sar, 8-ala angiotensin II, an angiotensin II receptor antagonist (AIIA) could prevent and reverse the vasoconstriction and resulting reduction in SNGFR with benzolamide. Benzolamide administration to hydropenic rats decreased SNGFR by 5.0±1.3 nl/min and AIIA infusion in these rats completely restored SNGFR to the control, prebenzolamide values. These results occurred when SNGFR was measured in both proximal and distal tubules. In another group of hydropenic rats prior AIIA infusion completely prevented any alteration in SNGFR with benzolamide administration (33.0±2.8 vs. 32.3±1.5 nl/min). Benzolamide administration did increase the late proximal tubular flow rate during AIIA infusion (17.2±1.1 to 23.4±1.1 nl/min,P<0.01), demonstrating that AIIA did not act by preventing the diuretic action of benzolamide in the proximal tubule. AIIA infusion alone did not alter control SNGFR or nephron plasma flow, suggesting that the effect of AIIA was not that of a non-specific vasodilator. These studies suggest that the renal vasoconstriction and reduction in SNGFR which results from benzolamide administration is mediated by the local action of angiotensin II.     

The cause of a depressed glomerular filtration rate after an ischaemic insult: whole kidney and superficial nephron study in the dog

Twenty-four hours after 90 min clamping of the left renal artery in dogs, the glomerular filtration rate (GFR) was decreased in the whole kidney (0.34 ml.min^–1g KW^–1 [KW=Kidney weight] vs 0.64 in contralateral unclamped kidney) just as in the single nephron (SNGFR, 19.7 vs 51.8 nl.min^–1). Renal blood flow (RBF) did not change; single nephron glomerular blood flow (SNGBF) was decreased by 9% only. After injection of Lissamine green into the renal artery, brief diffuse tinting of the whole kidney surface was observed. Thereafter, patchy coloration — corresponding to passage of the dye through patent tubuli — took place in approximately one-quarter to one-third of the kidney surface. Micropuncture measurements were carried out in these areas.The values of hydraulic pressure in peritubular capillaries and proximal convolutions were not different from those found in controls; directly measured glomerular capillary pressure was decreased (48.7 vs 59.5 mmHg). The ultrafiltration coefficient(K _f) was significantly depressed (2.7 vs 3.8 mmHg.nl^–1.min). Total kidney and arteriolar resistances remained unchanged but afferent resistance (R _A) was elevated (11%) and efferent resistance (R _E) was lowered (23%) compared with those of controls. Ninetyseven percent of proximally microinjected ³H-inulin was recovered from the control kidney but only 85 % from the kidney rendered ischaemic. In conclusion, the typical findings at 24 h after 90 min ischaemia are low GFR and SNGFR with normal RBF and almost normal superficial SNGBF values. This phenomenon is mainly due to a decrease in K _f and a decrease in R _E with a simultaneous increase in R _A; back-leak through damaged tubuli seems to play only a minor role.     

Influence of parathyroid hormone on glomerular ultrafiltration in the rat

Experiments were performed on 22 plasma-expanded Munich-Wistar rats to investigated the effects of parathyroid hormone (PTH) on the determinants of glomerular ultrafiltration. Mean values for single nephron filtration rate (SNGFR), glomerular plasma flow rate (QA), systemic oncotic pressure, and transglomerular hydraulic pressure difference (deltaP) were similar in acutely thyroparathyroidectomized (TPTX) rats and non-TPTX rats. Nevertheless, the glomerular capillary ultrafiltration coefficient (Kf) was uniformly higher in TPTX rats (greater than 0.113 +/- 0.005 (SE) nl/(s.mmHg)] than in non-TPTX controls (0.088 +/- 0.005). In TPTX rats, infusion of a submaximal dose (1 U/kg per min) of PTH resulted in significant decreases in SNGFR at constant QA and deltaP, due primarily to return of Kf to non-TPTX levels. Infusion of 10 U/kg per min of PTH to non-TPTX rats further reduced Kf, on average to 0.042 +/- 0.001 nl/(s.mmHg), leading to further reduction in SNGFR, whereas QA and deltaP again remained constant. These findings suggest that PTH may play an important role in modulating Kf, and consequently, SNGFR.     

Consistency of nephron filtration measurements by collection of total tubular fluid from different proximal sites

The stability of single nephron glomerular filtration rate (SNGFR) is assured by specific mechanisms such as the tubulo-glomerular feedback system and autoregulation. Studies on renal physiology rely heavily on the measurements of SNGFR, which are feasible only in animals. The measurement of SNGFR by collection of total tubular fluid may be influenced by the fall in intratubular hydrostatic pressure that may reflect the negative pressure applied to the sampling pipette. This effect may become more important with shortening of the distance between the sampling site and the Bowman space. We analysed this putative effect by performing collections of total tubular fluid from the late proximal (LP), and then from the early proximal (EP) segment of the same nephrons. In 128 paired collections LP-SNGFR averaged 35 (SEM 2) nl?·?min^?1, and was no different from the paired mean EP-SNGFR of 37 (SEM 2) nl?·?min^?1, P>0.179. Then EP- and LP- SNGFR were significantly correlated (r=0.77, P<0.001). As expected, the respective paired means of absolute and percentage reabsorptions, and those of collection rates were significantly different. The average SNGFR computed from each LP and EP paired measurement was significantly correlated with the simultaneously measured kidney glomerular filtration rate, GFR (r=0.60, P<0.0001). The ratio of GFR to SNGFR indicated the expected number of glomeruli. These data would indicate that the sampling site does not influence the measurement of SNGFR in the proximal tubule when the total fluid collection technique is correctly performed. They also exclude a time-dependent activation of the macula densa capable of upregulating SNGFR within the interval elapsing between the beginning of LP and the completion of EP collections, which in our study averaged 4.4 (SEM 0.1) min.     

Kinetics of the Glomerular Ultrafiltration in the Rat Kidney. An Experimental Study

The quantitative relation between the driving forces over the glomerular membrane and the glomerular plasma flow, on the one hand, and the single glomerular filtration rate (SNGFR), on the other, is still uncertain. Micropuncture measurements on Sprague-Dawley rats made it possible to calculate the net driving force over the glomerular membrane. The single glomerular plasma flow was determined from SNGFR and the single nephron filtration fraction (SNFF). The effective plasma flow was measured with PAH for total kidney and for superficial nephrons. The mean glomerular capillary pressure was found to be 62.6 mm Hg. The results indicate a net driving force of about 13 mm Hg at the distal end of the glomerular capillary. SNGFR was found to be 14.1 nl/min.100 g. SNFF amounted to about 0.27. The filtration fractions determined with the PAH method were in the same range. The results indicate a filtration disequilibrium, in contrast to those of Brenner et al. from measurements on a mutant Wistar rat strain. The filtration fractions seemed to be the same in all glomerular populations. It is clear that the SNGFR is pressure dependent. Our earlier findings of a nonautoregulation of the blood flow through the outer glomeruli were also confirmed.     

The effect of kinin and prostaglandin inhibitors on the renal response to angiotensin-converting enzyme inhibition: a micropuncture study in the dog

It has been suggested that angiotensin-converting enzyme (ACE) inhibition is accompanied by enhanced bradykinin and prostaglandin activities, which may contribute to the renal haemodynamic actions of ACE inhibitors. Therefore we investigated renal function by clearance and micropuncture techniques in dogs maintained either on normal or low-salt diet before and after ACE inhibition with an i. v. bolus of 0.1 mg/kg ramiprilat followed by an infusion of 5 μg kg⁻¹ min⁻¹. Subgroups each comprising six dogs were also treated with either HOE-140, a bradykinin B₂ receptor antagonist, or the cyclooxygenase inhibitor indomethacin. In general, renal effects of ramiprilat were more pronounced in dogs fed on low salt than in those on normal diet. In dogs on low salt, the mean arterial pressure decreased by 20% 20 min after ramiprilat application, whereas the total renal blood flow rose by 71% from 4.71 to 8.06 ml min⁻¹ g kidney weight⁻¹ and the glomerular filtration rate (GFR) by 28% from 0.74 to 0.95 ml min⁻¹ g⁻¹. Single-nephron glomerular blood flow and single-nephron GFR rose by 55% and 23% respectively. The total and the single-nephron filtration fraction decreased by 25% and 23% respectively. There were no substantial changes in glomerular and peritubular capillary and tubular pressures, but a significant increase in the ultrafiltration coefficient, K _f, by 103% from 3.55 nl/ mmHg to 7.19 nl/mmHg (26.7–54.0 nl/kPa) was observed. Afferent and efferent arteriolar resistances decreased in parallel by 55% and 47%. Prior and concomitant intrarenal arterial infusion of HOE-140 at a dose that blocked the vasodilatory effect of 9 ng kg⁻¹ min⁻¹ bradykinin had no significant effects in dogs on low salt but attenuated the relative rise in renal and single-nephron glomerular blood flow and K _f by 21%, 27% and 26% respectively in dogs on low salt (P<0.01). No such effects were observed with indomethacin. We conclude that ACE inhibition in the dog results in a parallel decrease in afferent and efferent resistance and significantly increases K _f. This latter effect is partly mediated by the kinin system under conditions of Na⁺ depletion.     

Autoregulation of nephron filtration rate in the dog assessed by indicator-dilution technique.

Micropuncture studies were conducted in anesthetized dogs to evaluate single nephron glomerular filtrate rate (SNGFR) and SNGFR autoregulation when assessed by means of an indicator-dilution technique (SNGFRID), which does not require interruption of distal volume delivery. In 18 dogs, control renal arterial pressure was 124 +/- 11 mmHg (SD), renal blood flow (RBF) was 185 +/- 58 ml/min, and whole kidney GRF was 37 +/- 7 ml/min. SNGFRID averaged 57 +/- 15 nl/min and was significantly lower than SNGFR determined on the basis of total collections (SNGFRTC) from proximal tubules (75 +/- 17 nl/min). However, SNGFRID was not significantly different from the overall average SNGFR of 62 +/- 12 nl/min estimated from whole kidney GFR and the total number of glomeruli (613,000 +/- 74,000). In 10 animals, renal arterial pressure was reduced to an average of 94 +/- 8 mmHg; whole kidney autoregulation was highly efficient and average RBF and GRF remained within 1 and 3% of their control values. Likewise, SNGFRID was not significantly altered at 52 +/- 17 and 52 +/- 16 nl/min. In contrast, SNGFRTC decreased significantly from 72 +/- 17 to 51 +/- 13 nl/min. These results indicate that the indicator-dilution technique provides a reliable assessment of SNGFR and allows the manifestation of single nephron autoregulatory behavior. They provide further support for the hypothesis that maintenance of distal volume delivery may be a necessary aspect of the autoregulation phenomenon.     

Time-dependent heterogeneity of filtration rate in the autoreguiating rat kidney

Experiments were performed to study the regulation of the single-nephron glomerular filtration rate (SNGFR) in superficial and juxtamedullary nephrons, as the left kidney of Sprague Dawley rats was submitted to a reduced arterial pressure of 70 mmHg by means of an aortic clamp. The SNGFR at different cortical levels was measured 0.5, 1, 5, 20 or 45 min after the reduction, in order to ascertain whether the effects of the regulatory mechanisms are modified with time. A Hanssen technique was used, which allows one determination of filtration rates per animal. At a renal arterial pressure (RAP) of 100 mmHg (= control animals) the SNGFR amounted to 20±1.2 and 23± 0.8 nlmin^-1–g^-1 kidney weight in the outer and inner cortical (OC, IC) nephrons. When RAP was further reduced to 70 mmHg, the autoregulation of SNGFR, determined after 0.5 min, was highly efficient for both OC and IC nephrons (19 ± 2.0, 23 ± 2.6). A prolonged reduction in RAP caused a gradual decline in SNGFR. The filtration rate measured after 5 min was 15 ±1.4 for OC and 20 ± 1.8 for IC nephrons. The decline was most pronounced for OC nephrons, which led to a fractional redistribution in favour of IC nephrons. Thus, SNGFR_IC/SNGFR_oc was 1.16± 0.065 when RAP was 100 mmHg and 1.41 ± 0.126 after 5 min with an RAP of 70 mmHg. It is well documented that suprarenal aortic occlusion is a powerful stimulus for the release of renin. This was manifested as an increase in the arterial pressure proximal to the aortic clamp. The fractional redistribution to IC nephrons and the loss of autoregulation, when the renal hypotension was sustained, may be an expression of the intrarenal mechanisms attempting to restore RAP. It is likely that the renin/angiotensin system is involved in these processes.     

Activation of the tubuloglomerular feedback mechanism in dehydrated rats

To study the influence of the tubuloglomerular feedback control (TGF) on the regulation of glomerular filtration rate (GFR) during dehydration, micropuncture experiments were performed on surface nephrons of dehydrated rats. Dehydration was achieved by withdrawal of food and water for 24 h. The urine flow rate decreased to 1.5 μl/min (controls 2.9 μl/min) and GFR decreased in these rats to 0.80 ml/min (controls 1.22). TGF was studied by two different micropuncture procedures. With the first technique the changes in proximal stop-flow pressure in response to changes of the late proximal microperfusion rate were measured. With this technique the perfusion rate necessary to induce a half maximal stop-flow pressure response, the turning point, was also determined. An increased TGF sensitivity was found in dehydrated rats, as indicated by increased stop-flow pressure responses (35 versus 26%) and decreased turning points (16 versus 21 nl/min). With the second micropuncture technique the single nephron GFR (SNGFR) was measured at distal and proximal tubular sites, in the same nephron. Distal SNGFR was decreased during dehydration to 32.2 nl/min, versus 42.7 nl/min in controls. A significant difference between paired SNGFR measurements in the same nephron was observed during dehydration, the proximal value being 5.3 nl/min higher than the distal, whereas this difference was not seen in control rats. This finding indicates that activation of the feedback mechanism takes place to reduce SNGFR. It is concluded that the decrease in whole kidney GFR is partly caused by the observed increase in feedback activity. The present results are also in agreement with our earlier hypothesis that the hydrostatic and oncotic pressure conditions within the interstitial space surrounding the macula densa cells modulate the sensitivity of the tubuloglomerular feedback mechanism.     

Renal function in normal and potassium-depleted rats before and after preparation for micropuncture experimentation

Renal function was examined in unrestrained conscious rats maintained on either a control diet or a low-potassium diet, then re-examined in the same animals after thiobutabarbital (Inactin) anaesthesia and preparation for micropuncture studies. In conscious rats, inulin clearance (C_In) was not significantly different in the two groups (control 1012±43, low-K 904±58 l/min per 100g body wt; mean±SE), but lithium clearance (C _Li; used as an estimate of end-proximal fluid delivery) and fractional lithium excretion (FE_Li) were substantially reduced in the low-K group (C _Li: 246±11 vs 126±8 l/min per 100g body wt, P<0.001; FE_Li: 0.245±0.009 vs 0.143±0.008, P<0.001). Following anaesthesia and preparation for micropuncture, there were significant reductions in urine flow rate and sodium excretion in the control group, but not in the low-K rats. Potassium excretion increased in both groups, but values in the potassium-depleted animals remained extremely low. In neither group of rats was preparation for micropuncture associated with significant changes in C _In, C _Li or FE_Li. Thus, differences in tubular function between control and potassium-depleted rats were still apparent. The results suggest that preparation for micropuncture disturbs the function of the distal nephron, but that rates of glomerular filtration and proximal tubular reabsorption remain similar to values in conscious animals.     

The effect of two different calcium antagonists on the glomerular haemodynamics in the dog

Kidney function of beagles fed a constant amount of food containing 3 mmol sodium.kgbodywt⁻¹.day⁻¹, and anaesthetized with pentobarbitone was investigated by clearance and micropuncture techniques during an intrarenal infusion of saline or the calcium antagonists verapamil (VER, 4 μg.kgbodywt⁻¹.min⁻¹) or nifedipine (NIF, 0.3 μg.kgbodywt⁻¹.min⁻¹). Neither drug changed the mean arterial pressure. Apart from the natriuresis and diuresis, which were significantly greater with NIF than with VER, the response to both drugs was similar. Increases in renal blood flow (RBF; 17% with VER, 20% with NIF), glomerular filtration rate (GFR; VER: 34%; NIF: 39%) and filtration fraction (VER: 12%; NIF: 14%) were observed; similar values were obtained at the single nephron level. Pressure in glomerular capillaries, measured directly after ablation of a thin layer of cortex corticis, was increased by 11% with VER and 10% with NIF; no changes in proximal tubular and peritubular capillary pressure were seen. The glomerular ultrafiltration coefficient (K_f) did not change with either drug. Total arteriolar resistance was decreased (VER: 20%; NIF: 15%) due to a decrease in afferent resistance (VER: 31%; NIF: 27%) with no corresponding change in efferent resistance. The cause of the lack of responsiveness of the efferent arteriole remains unclear. In conclusion, in acute experiments with intrarenal administration, both drugs increase RBF and GFR by a preferential afferent dilatory mechanism without any change in K_f.     

Intrarenal haemodynamic and glomerular responses to inhibition of nitric oxide formation in rabbits.

1. The renal effects of inhibiting nitric oxide (NO) formation using N-nitro-L-arginine (NOLA, 20 mg kg-1) were examined using micropuncture techniques in pentobarbitone-anaesthetized rabbits. 2. Renal vascular resistance doubled from 2.7 +/- 0.5 to 5.0 +/- 1.1 mmHg ml-1 min-1 after NOLA (P < 0.01), with similar percentage increases in both pre- (149 +/- 38%, P < 0.01) and postglomerular (158 +/- 42%, P < 0.01) resistance. 3. Glomerular capillary pressure rose from 33 +/- 1 to 40 +/- 1 mmHg after NOLA (P < 0.01) but despite this, glomerular filtration rate (GFR) and single nephron glomerular filtration rate did not significantly change. 4. Blood pressure increased 18 +/- 1 mmHg (P < 0.001) within 10 min of NOLA administration and remained near this level for the next 90 min. 5. The glomerular ultrafiltration coefficient (Kf) decreased significantly from 0.085 +/- 0.022 to 0.035 +/- 0.006 nl s-1 mmHg-1 (P < 0.05). 6. Urine flow and sodium excretion increased markedly (26 +/- 9 to 337 +/- 102 microliters min-1 and 5 +/- 2 to 342 +/- 12 mumol min-1 respectively, (P < 0.001)) and sodium fractional excretion rose from 1.0 +/- 0.3 to 8.0 +/- 2.2% (P < 0.01). 7. Thus, administration of NOLA to rabbits caused vasoconstriction of both pre- and postglomerular vessels, diuresis and natriuresis without significant change in GFR, and a reduction in Kf. The results suggest that NO may play an important role in the regulation of renal haemodynamics and glomerular function.     

The effect of pressor doses of Angiotensin II on autoregulation and intrarenal distribution of glomerular filtration rate in the rat

This study was designed to investigate the effect of pressor doses of exogenous Angiotensin II (AII) on autoregulation and intrarenal distribution of single nephron glomerular filtration rate (SNGFR) in anesthetized, normotensive rats. SNGFR at all cortical levels of the left kidney was measured with a modified Hanssen technique at three renal arterial pressures (RAP): Spontaneous, 100±1 mmHg and 70±1 mmHg. In control rats, both outer cortical (OC) and inner cortical (IC) nephrons showed complete autoregulation of SNGFR when RAP was redced to 100±1 mmHg. Further reduction to 70±1 mmHg resulted in different responses among the cortical layers, accompanying a decrease in SNGFR.The SNGFR_Ic/SNGFR_oc ratio increased from 1.36±0.053 to 1.52±0.047 and a fractional redistribution of glomerular filtration rate towards IC nephrons was seen. When the kidney was submitted to a RAP of 70±1 mmHg, there was a concomitant increase in central arterial pressure (CAP) from 120±4.3 to 134±3.2 mmHg. A continuous i. v.infusion of All (0.5 μg · min^-1· kg^-1 BW) increased mean arterial pressure from 123±1.4 to 142±3.8 mmHg, an effect corresponding to that on peripheral vascular resistance during reduction of RAP to 70±1 mmHg in control rats. This dose reduced SNGFR at all cortical levels, but did not per se lead to redistribution of SNGFR.A reduction in RAP to 100±1 mmHg during All administration resulted in impaired autoregulation of SNGFR in both OC and IC nephrons. Our results show that exogenous All impairs autoregulation and cannot per se have an effect mimicking the fractional redistribution seen in control rats with a reduction of RAP below the limit for autoregulation. However, in this situation intrarenally formed All may still be of importance for autoregulation and distribution of glomerular filtration rate.     

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.     

Maturational development of glomerular ultrafiltration in the rat.

To ascertain the cause of low glomerular filtration rate in newborn and immature mammals, we measured glomerular pressures and flows directly in immature (30- to 45-day-old) euvolemic Munich-Wistar rats with surface glomeruli. As with total kidney GFR, single nephron (SN)GFR was found to be significantly lower than in adult rats, on average by 40% when corrected for kidney weight. Equality between efferent oncotic pressure and transglomeruler hydraulic pressure difference (deltaP) was usually achieved in immature rats, indicating that the glomerular capillary ultrafiltration coefficient is not a factor limiting SNGFR and GFR in immature rats. Although the average values for deltaP in immature rats were slightly, albeit significantly, lower than in adults, markedly lower values (79 +/- 5 vs. 136 +/- 10 nl/min per g kidney wt) for glomerular plasma flow rate (QA) proved to be the primary factor responsible for the lower SNGFR and GFR values in immature rats. Considerably higher values for afferent and efferent arteriolar resistances contributed to this low QA state in immature rats.     

The influence of long-term infusion of the calcium antagonist diltiazem on postischemic acute renal failure in conscious dogs

Summary The influence of long-term infusion of the calcium-entry blocker diltiazem on postischemic acute renal failure was investigated in conscious dogs monitored by implanted instruments. In 18 uninephrectomized beagle dogs on a salt-rich diet, an electromagnetic flow probe and an inflatable plastic cuff were placed around the renal artery. Acute renal failure was induced by inflating the cuff for 180 min in the conscious animal. Group A (n=5, control) received an intraaortic injection of 0.9% NaCl (5 ml/day) from the 3rd day before until the 7th day after ischemia and group B (n=6, posttreatment) an intra-aortic injection of diltizem (5 µg·min^–1·kg^–1) beginning at the end of ischemia until the 7th day. Group C (n=7, pre- and posttreatment) received diltiazem from the 3rd day before until the 7th day after ischemia. In group A, renal blood flow dropped from 149±16 (preischemic) to 129±29 ml·min^–1 on the 1st day after ischemia. In contrast, renal blood flow increased on the 1st postischemic day in both treatment groups by 29±15% (group B,P 0.05) and 14±13% (group C). In the following days, there was no significant difference in renal blood flow between groups A, B and C. In group B, the reduction of the glomerular filtration rate was similar to that in the control group. In group C, the glomerular filtration rate was significantly less reduced than in group A (34±1.8 preischemically to 17±5.4 on day 1,P 0.05 and 20±4.1 ml·min^–1 on day 7,P 0.05). Plasma renin activity increased in both diltiazem groups, more pronounced so in group B (from 3.7±1.0 on day 1 to 16.2±7.9 ng ATI·ml^–1·h^–1 on day 7,P 0.05). In contrast to groups A and B, the increase in fractional sodium excretion was less pronounced in group C. Likewise, the decrease in free water-reabsorption was less marked than in groups A or B. It was apparent that diltiazem, when administered pre- and post-ischemically, preserved glomerular filtration rate and renal blood flow. When diltizem was given solely postischemically there was an improvement in renal blood flow, but no significant influence on glomerular filtration rate. We therefore conclude that mainly tubular factors, in addition to the attenuation of postischemic vasoconstriction, are involved in the protective effect of diltiazem on postischemic acute renal failure in conscious dogs.Abbreviations ARF acute renal failure - C_osmol clearance of osmolarity - E_Na urinary excretion rate of sodium - FE_Na fractional excretion rate of sodium - GFR glomerular filtration rate - HR heart rate - NE norepinephrine - PAM mean arterial blood pressure - PRA plasma renin activity - RBF renal blood flow - RVR renal vascular resistance - T_H2_O free water reabsorption - V_U urine volume