Dynamics of glomerular ultrafiltration in Amphiuma means

To study renal function inAmphiuma means, the hydrostatic pressures in vascular and tubular structures and the glomerular filtration rate were determined at different arterial blood pressures. In the arterial blood pressure range studied no evidence of autoregulation of the glomerular capillary pressure or of the hydrostatic pressure gradient over the capillary membrane was found. The glomerular filtration ceases at an arterial blood pressure below 12 cm H₂O. No significant difference between tubular free flow pressure and peritubular capillary pressure was noted. Furthermore, it was found that the glomerular capillary pressure could be estimated by measuring the intratubular stop-flow pressure and arterial colloid osmotic pressure at an arterial pressure above 15 cm H₂O. It was also found possible to measure the glomerular capillary pressure at the very end of the afferent arteriole. The protein concentrations in afferent and efferent arteriolar blood were determined and the colloid osmotic pressures were calculated according to a new formula derived forAmphiuma plasma. The dynamics of glomerular ultrafiltration was evaluated. A filtration equilibrium across the glomerular membrane was reached, since the efferent colloid osmotic pressure was not significantly different from the hydrostatic pressure gradient across the glomerular capillary membrane.     

Renal interstitial pressure and tubuloglomerular feedback control in rats during infusion of atrial natriuretic peptide (ANP)

Atrial natriuretic peptide (ANP), injected at physiological concentrations, is known to induce both natriuresis and diuresis. It has been suggested by some investigators that these changes result from an increasing glomerular filtration rate (GFR), but others have been unable to demonstrate an increased GFR. The tubuloglomerular feedback (TGF) mechanism is an important regulator of GFR, and the sensitivity of TGF is decreased during ANP administration. Furthermore, resetting of TGF is, in most instances, related to changes in renal interstitial hydrostatic and oncotic pressures. It is also known that ANP may increase capillary permeability which may change renal interstitial pressure. The present study was performed to examine renal interstitial pressures and the TGF mechanism during ANP infusion. In accordance with previous studies, TGF sensitivity was found to be decreased. The tubular flow rate which elicited half the maximal drop in stop-flow pressure (P_sf) was increased from 18.5 to 25.7 nl min^-1. In contrast, ANP infusion resulted in a decreased interstitial hydrostatic pressure and an increased interstitial oncotic pressure. From previous experiments, such changes in interstitial pressures would be expected to increase TGF sensitivity. The changes in interstitial pressure cannot, therefore, directly explain the resetting of the feedback mechanism. In conclusion, the present paper shows a decreased renal net interstial pressure after intravenous administration of ANP.     

Reduced permselectivity in isolated perfused rat kidneys following small elevations of glomerular capillary pressure

A modified rat kidney preparation was used to explore how changes in hydrostatic pressure affect the permselective properties of the glomerular capillary bed. Th? maximally vasodilated kidneys of 18 rats were perfused with albumin solutions (16.7 g ^-1) at different flow rates and hence arterial pressures (P_A). One kidney in each rat was exposed to pressure elevations with the other kidney serving as a control perfused at constant P_A of about 100 mmHg. Both the vascular resistance to flow and the glomerular filtration rate (GFR 34.6 ± 2.9 ml min¹ 100 g^_1) were similar in the two kidneys at equal P_A and remained constant throughout the experiment. The ratio of albumin clearance over GFR (Θ) was initially around 0.4% at constant P_A and gradually increased during 1.5 h to reach 0.7% at the end of the experiment. A direct increase of P_A from 100 to 200 mmHg for 15 min resulted in a calculated increase of the effective glomerular filtration pressure gradient of 10–15 mmHg and in a two-fold increase ofΘ when measured at an identical P_A of 100 mmHg. Albumin clearance was almost fully normalized within 20 min similar to that observed in e.g. skeletal muscle. However, the glomerular capillary barrier seemed to be far more sensitive to elevations of hydrostatic pressure than other capillary walls which require capillary pressure increments of 60 mmHg in order to induce similar reversible changes in permeability. Therefore, we conclude that an elevated P_G:c per se induces changes of glomerular permselectivity, which may have important pathophysiological implications during conditions of proteinuria.     

Renal autoregulation: evidence for the transmural pressure hypothesis.

Autoregulation of glomerular filtration rate (GFR) was examined during uteral orarterial constriction in anesthetized dogs after renal denervation. GFR was sustaineduntil ureteral pressure greater than 80 mmHg, provided renal arterial pressure exceeded 180 mmHg, but fell at ureteral pressure less than 54 mmHg when arterial pressure averaged 127 plus or minus 5 mmHg; renal blood rose as GFR declined. Ethacrynic acid, saline, or mannitol infusion increased tubular pressure without reducing GFR,but during subsequent ureteral constriction GFR fell at uteral pressure less than 40mmHg. During arterial constriction GFR was maintained at lower arterial pressures in hydropenic than in diuretic dogs. Because of thisdifference in the range of autoregulation, saline infusion increased GFR more in hydropenic than in diuretic dogs except at high arterial pressure. This response to reduced plasma oncotic pressure and the constancy of GFR over a wide range of proximal tubular and arterial pressure indicate constancy of thehydrostatic transmural pressure of glomerular capillaries. Afferent arteriolar resistance is, in addition to a regulation by transmural pressure, perhaps controlled by vascular stretch receptors in the glomeruli.     

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.     

Intratubular and peritubular capillary hydrostatic and oncotic pressures after chronic renal sympathectomy in the anaesthetized rat

The possible role of peritubular capillary physical forces in the diuretic-natriuretic effects of chronic renal denervation was investigated in Inactin-anaesthetized non-diuretic control (C) and unilaterally denervated (D) rats. Micropuncture techniques were combined with measurement of intratubular and peritubular capillary hydrostatic pressures and afferent and efferent arteriolar plasma oncotic pressures were determined, as well. Compared to data of C rats and of innervated kidneys, marked denervation diuresis and natriuresis were seen without changes in GFR. Both late proximal and early distal (F/P)_In values were significantly lower in D kidneys with similar SNGFR. Afferent (π_a) and efferent (π_e) arteriolar oncotic pressures were unchanged by denervation (C-π_a = 23.3 ± 0.79, π_e = 29.9 ± 0.87 mm Hg; D-π_a = 23.2 ± 0.94, π_e = 29.8 ± 1.04 mm Hg). Proximal intratubular hydrostatic pressure was moderately but significantly higher in D kidneys (C=11.9±0.5, D=13.7±0.3 mm Hg,P<0.01), while peritubular capillary pressures were: efferent arteriole (C=13.9±0.5, D=13.4±0.6 mm Hg, NS). It is concluded that the tubular effects of chronic renal sympathectomy are not dependent on changes in Starling forces of the peritubular environment.     

Renal interstitial pressure and tubuloglomerular feedback control in rats during infusion of atrial natriuretic peptide (ANP).

Atrial natriuretic peptide (ANP), injected at physiological concentrations, is known to induce both natriuresis and diuresis. It has been suggested by some investigators that these changes result from an increasing glomerular filtration rate (GFR), but others have been unable to demonstrate an increased GFR. The tubuloglomerular feedback (TGF) mechanism is an important regulator of GFR, and the sensitivity of TGF is decreased during ANP administration. Furthermore, resetting of TGF is, in most instances, related to changes in renal interstitial hydrostatic and oncotic pressures. It is also known that ANP may increase capillary permeability which may change renal interstitial pressure. The present study was performed to examine renal interstitial pressures and the TGF mechanism during ANP infusion. In accordance with previous studies, TGF sensitivity was found to be decreased. The tubular flow rate which elicited half the maximal drop in stop-flow pressure (Psf) was increased from 18.5 to 25.7 nl min-1. In contrast, ANP infusion resulted in a decreased interstitial hydrostatic pressure and an increased interstitial oncotic pressure. From previous experiments, such changes in interstitial pressures would be expected to increase TGF sensitivity. The changes in interstitial pressure cannot, therefore, directly explain the resetting of the feedback mechanism. In conclusion, the present paper shows a decreased renal net interstitial pressure after intravenous administration of ANP.     

Two models of glomerular filtration rate and renal blood flow in the rat

Two mathematical models of glomerular filtration and blood flow are derived. The first is based on principles of fluid and mass conservation in individual capillaries. The model explains why the filtration rate (GFR) is strongly dependent on local hydrostatic and protein oncotic pressures, and on plasma flow rate (GCPF), but only weakly dependent on exact numbers, lengths, radii, or filtration coefficient of glomerular capillaries. The model shows that much of the increased GFR in both isooncotic plasma loading and isotonic Ringer's loading is due to increased GCPF caused by diluting erythrocytes. The second model uses several approximations and reduces to a quadratic in afferent arteriolar blood flow. When arterial pressure, hematocrit, plasma protein concentration, and afferent and efferent arteriolar resistances are specified, the model predicts GFR, afferent arteriolar blood flow, and filtration fraction. Alternatively, if any two of these three variables are known, the model predicts segmental arteriolar resistances. The model indicates that GFR and blood flow regulation must be located in the afferent arteriole, despite the strong dependence of GFR on GCPF.     

Hemodynamic mechanisms influencing sodium excretion during angiotensin infusion.

To examine mechanisms of transition between antinatriuresis and natriuresis, angiotensin II was first infused intrarenally (0.001-0.07 mug/kg-min) in anesthetized dogs; glomerular filtration rate (GFR), sodium excretion, and intrarenal pressure (IRP), indicating tubular pressure, fell as during mechanical aortic constriction. During supplementary intravenous infusion (0.10-0.30 mug/kg-min), renal blood flow (RBF) rose toward control (tachyphylaxis). Tubular reabsorption increased but was still 17.1% below control. Filtration fraction averaging 0.31 remained constant. Sodium excretion and IRP exceeded control but were normalized by restoring renal arterial pressure mechanically. During intrarenal angiotensin infusion, carotid constriction increased blood pressure more, but RBF, IRP, and sodium excretion less than intravenous angiotensin. Intrarenal infusion of angiotensin at 0.10-0.20 mug/kg-min increased RBF and sodium excretion more in infused than in contralateral kidneys. Thus, angiotensin natriuresis depends on increased perfusion pressure and is augmented as tachyphylaxis develops. High correlation between sodium excretion and IRP at unchanged filtration fraction suggests a regulation of sodium excretion by hydrostatic rather than oncotic pressures in glomerular and peritubular capillaries.     

Renal response to volume depletion and expansion in Milan hypertensive rats

In previous studies on Milan hypertensive (MHS) rats, we found an impaired tubuloglomerular feedback (TGF) response before, during and after development of hypertension. In the present study MHS rats and rats of the Milan normotensive strain (MNS) were investigated after 24 hours of volume depletion (VD) and subsequently after 5% isotonic volume expansion (VE) with respect to whole kidney function, interstitial hydrostatic (P_int) and oncotic (II_int) pressures, stop-flow pressure characteristics of TGF and changes in early proximal flow rate in response to increased loop of Henle flow. MHS rats had higher mean arterial blood pressure (P_a) than MNS rats (129 vs. 101 mmHg) both after VD and after subsequent VE. No difference in glomerular filtration rate (GFR) was found. Both strains had a low urine flow rate (1.5 μl min^-1) during VD, which increased fourfold after VE. The interstitium was significantly more dehydrated in MHS, as indicated by a more negative net interstitial pressure (P_int–±_int t than in MNS (-1.3 ± 0.3 vs. ± 0.0 ± 0.5 mmHg) after VE. The TGF mechanism was more activated in MHS during volume depletion, as indicated by a larger drop in stop-flow pressure (P_sf) in response to loop of Henle perfusion (7.1 ± 0.7 vs. 4.7 ± 0.2 mmHg, P < 0.05). However, during VD the loop of Henle flow that elicited half maximal response in P_sf, the turning point (TP), was equally low in MHS and MNS (13.5 ± 0.6 and 14.3 ± 0.4, respectively). After VE, however, TP increased significantly more in MNS to (32.6 ± 2.1 nl min^-1) then in MHS (to 21.8 ± 0.9 nl min^-1, P < 0.05). It is concluded that the blunting of the TGF resetting in response to VE in MHS rats may well be of importance in the development of hypertension in the MHS strain.     

Kinetics of the Glomerular Ultrafiltration in the Rat Kidney. A Theoretical Study

The glomerular filtration process was evaluated theoretically from micropuncture data obtained from Sprague-Dawley rats. The hydrostatic pressures in the glomerular capillaries and Bowman's space minus the oncotic pressure in systemic plasma gave the net driving force at the proximal end of the glomerular capillary. From the single nephron filtration fraction the mean net driving force over the glomerular membrane was calculated to be 20 mm Hg during normotension, decreasing to 12 mm Hg during a perfusion pressure of 80 mm Hg. The hydraulic permeability for one glomerulus was 0.7-0.8 nl/min. 100g b. wt. mmHg. The pressures at the distal end of the glomerular capillaries were 13 and 6 mm Hg under the above two conditions, indicating non-equilibrium of the filtration process at the end of the glomerular capillary. It was shown that the glomerular filtration rate is mainly influenced by the driving pressures. During hypotension an increased plasma flow dependency was evident. Brenner et al. found a filtration equilibrium and a plasma flow dependent glomerular filtration rate in a mutant Wistar rat strain. The discrepancy between their results and ours is due to the low glomerular plasma flow and hydrostatic pressures in the Wistar rats. It is concluded from our results that both pre- and postglomerular resistances may influence the glomerular filtration rate and glomerular plasma flow independently.     

A simple method for estimating tubular and net glomerular capillary pressures in the isolated perfused kidney

To estimate glomerular filter resistance it is necessary to measure net glomerular capillary pressure, tubular pressure, and glomerular filtration rate. Net glomerular capillary pressure is defined as the difference between glomerular capillary hydrostatic and oncotic pressures. A method has been developed for estimating both tubular pressure and net glomerular capillary pressure for the whole kidney from the time course of the rise in ureteral pressure on ureteral occlusion. Pressure and flow relations which apply in the kidney during ureteral occlusion have been represented by a simple mathematical model. Estimates of tubular pressure and net glomerular capillary pressure are made by representing the first 60 s of the rise in ureteral pressure as the linear combination of two exponential terms. These estimates compare favourably with corresponding results obtained from a more general numerical analysis. Direct measurements of tubular pressure and net glomerular capillary pressure made by micropuncture of early proximal tubules have been compared with analytical estimates from subsequent ureteral occulusion. There was no significant difference between results obtained using either method for a wide range of perfusion pressures.     

Proximal tubular stop flow pressure: an index of glomerular capillary pressure?

Central to the assumption that glomerular capillary pressure (P _gc) can be equated with the sum of arterial oncotic pressure ( _art) and the pressure in a blocked proximal tubule (stop flow pressure, P _sf) is that filtration ceases in the blocked nephron. Should filtration not cease, but continue at a rate equal to tubular reabsorption between the block and the glomerulus, P _sf, for a given P _gc, will depend on the distance between block and glomerulus. This would have serious consequences for the interpretation of P _sf, particularly in respect of its frequent use in analysis of the tubuloglomerular feedback (TGF) mechanism. Experiments were performed in anaesthetized Wistar rats to examine whether a length dependency of P _sf exists and, if so, to what extent this relationship alters during maximal TGF stimulation by loop of Henle perfusion. A length dependency of P _sf existed both in the absence and presence of loop flow. The regression coefficients were significantly different from 0 and from each other. P _gc cannot thus be equated with the sum of P _sf and _art. The length dependent error in P _sf makes it unsuitable for the quantitative analysis of TGF and glomerular haemodynamics.     

Tubular reabsorption and diabetes-induced glomerular hyperfiltration

Elevated glomerular filtration rate (GFR) is a common observation in early diabetes mellitus and closely correlates with the progression of diabetic nephropathy. Hyperfiltration has been explained to be the result of a reduced load of sodium and chloride passing macula densa, secondarily to an increased proximal reabsorption of glucose and sodium by the sodium-glucose co-transporters. This results in an inactivation of the tubuloglomerular feedback (TGF), leading to a reduced afferent arteriolar vasoconstriction and subsequently an increase in GFR. This hypothesis has recently been questioned due to the observation that adenosine A₁-receptor knockout mice, previously shown to lack a functional TGF mechanism, still display a pronounced hyperfiltration when diabetes is induced. Leyssac demonstrated in the 1960s (Acta Physiol Scand 58 , 1963:236) that GFR and proximal reabsorption can work independently of each other. Furthermore, by the use of micropuncture technique a reduced hydrostatic pressure in Bowman’s space or in the proximal tubule of diabetic rats has been observed. A reduced pressure in Bowman’s space will increase the pressure gradient over the filtration barrier and can contribute to the development of diabetic hyperfiltration. When inhibiting proximal reabsorption with a carbonic anhydrase inhibitor, GFR decreases and proximal tubular pressure increases. Measuring intratubular pressure allows a sufficient time resolution to reveal that net filtration pressure decreases before TGF is activated which highlights the importance of intratubular pressure as a regulator of GFR. Taken together, these results imply that the reduced intratubular pressure observed in diabetes might be crucial for the development of glomerular hyperfiltration.     

Impaired glomerular permselectivity for albumin in chemically medullectomized WKY rats

Chemical renal medullectomy with 2-bromo-ethylamine hydrobromide (BEA) has been used to study the importance of the renal medulla in blood pressure regulation. However, conclusive evidence as to whether BEA treatment affects the glomerular barrier is lacking. In the present study, the effects of BEA upon glomerular permselectivity for albumin were studied using isolated kidneys (IPK) perfused at a low temperature (8 °C) to inhibit tubular reabsorption of proteins. Sixteen WKY rats (W_B) received an i.v. injection of BEA (150 mg kg^-1) while 10 rats served as controls (W_C). Volume balance, urinary osmolality and creatinine clearance (GFR) were measured in metabolic cages. Acute paired experiments (n=9) were performed 5–7 weeks after BEA. The rats were anaesthetized and the total in vivo albumin excretion was recorded. The kidneys were then isolated and perfused for measurements of inulin clearance (GFR) and fractional albumin clearance without tubular reabsorption of protein. The nine BEA treated rats showed polyuria and hypoosmotic urine. In vivo GFR was lower in the BEA treated groups when measured with creatinine clearance (459±22 vs. 213±41 μL min^-1 100 g^-1 body wt, P<0.001), while GFR was not significantly changed in the IPK (W_C=135±27, W_B=92±14 μL min^-1 100 g^-1 body wt, n.s.) when perfused at identical pressures. The fractional albumin clearance was increased three times in the BEA group (W_B=9.6±3.4J, P<0.05). Moreover, albumin excretion in vivo was similar in the two groups despite low GFR in the BEA group. We conclude that BEA treatment affects glomerular permselectivity for albumin.     

Hydrostatic and oncotic pressures in the interstitium of dehydrated and volume expanded rats

The pressures in the renal interstitial space seem to have important influence on the setting of the sensitivity of the tubuloglomerular feedback that controls the glomerular filtration rate (GFR), and on the rate of proximal tubular fluid reabsorption. Measurements were made of interstitial pressure conditions, GFR, renal plasma flow (RPF), urinary excretion of sodium and potassium, and plasma renin activities in dehydrated animals and normopenic controls, before and after saline volume expansion (5% of body weight and hour). Colloid osmotic pressure, estimated from the protein concentration in renal hilar lymph, was 7.5 mmHg in the dehydrated animals (controls 2.8 mmHg) and decreased to 3.1 (controls 1.7 mmHg) after volume expansion. The lymph flow rate was increased in both groups of animals after volume expansion. Interstitial hydrostatic pressure, measured in the subcapsular space, was 2–3 mmHg in dehydrated and control animals and increased to 3–4 mmHg after volume expansion. In dehydrated rats GFR and RPF was reduced to 60% of the control values, but after volume expansion they regained control values. After volume expansion, urinary excretion of fluid and electrolytes increased more in controls than in dehydrated rats. Plasma renin activity was dereased in both groups of rats after volume expansion. Thus, in dehydrated animals there was a high colloid osmotic pressure and a low hydrostatic pressure in the renal interstitium, while after volume expansion the oncotic pressure fell and the hydrostatic pressure rose. The effect of volume expansion was found to be dependent on the preceding volume balance situation in the animal.     

Influence of glomerular filtration rate on renal PAH secretion rate in the rat kidney

PAH secretion (T_PAH) was studied in rats at spontaneously occurring glomerular filtration rate (GFR). At saturated transport, T_PAH was found to be correlated to GFR. This relationship was also observed at unsaturated transport where T_PAH depends upon the PAH concentration in arterial plasma. However, no significant correlation between T_PAH and renal PAH load or renal plasma flow rate was found when the effects of GFR were removed by partial correlation analysis. A dependency of T_PAH on GFR explains the correlations found between filtration fraction (FF) and renal PAH extraction (E_PAH) or renal tubular PAH extraction fraction (E_PAH-FF_PAH). Thus, even at low PAH concentration in a. plasma, renal PAH extraction may only be assumed to be constant if the filtration fraction is constant.     

Determination of segmental resistances in the canine kidney

Summary Series connected segmental resistances in the normal canine kidney were studied under free flow and under stop flow conditions. For the calculation of glomerular capillary pressure equation GFR =k (p _gl –p _ir –p _co) has been used. The permeability constant (k) was determined under the assumption that below the autoregulatory rangep _gl=p _art; supposing the independence ofk of perfusion pressure,p _gl could be calculated at any arterial pressure. Intrarenal deep venous pressure equals proximal tubular and peritubular capillary pressures in free flow; stabilized ureter occlusion pressure measures intrarenal pressures in stop flow.The procedure enables the determination of glomerular capillary pressure without recurring to ureter occlusion. Thusp _gl amounts to 88 mm Hg (free flow) and 96 mm Hg (stop flow) whereas the tranditional manner of calculation (p _ur-stop+p _co) yields 73 mm Hg for both conditions. Owing to intense residual filtrationp _gl exceedsp _ur-stop+p _co even under stop flow conditions.     

Effect of isotonic volume expansion on glomerular filtration rate and renal hemodynamics in the developing rat kidney

Young rats (20–24 days) and adult rats (4–5 days) were studied during hydropenia and volume expansion with regard to glomerular filtration rate (GFR) and the determinants of GFR. During hydropenia, GFR and renal blood flow (RBF) were significantly lower in younger than in adult rats both in absolute terms and when related to bodyweight. Equivalent degrees of volume expansion (6% of b. wt.) resulted in a much more pronounced increase in GFR and RBF in younger than in older rats. This suggests that the high renal vascular resistance in hydropenic young rats is primarily due to vasoconstriction. The relationship between the filtration rate of superficial nephrons and the total GFR was the same in hydropenic and volume expanded rats in both age groups. The tubular stop flow pressure, the calculated hydrostatic glomerular capillary pressure and ultrafiltration pressure in the afferent part of the glomerular capillaries was slightly lower in hydropenic young rats than in hydropenic adult rats. The pressures did not rise after volume expansion. It is concluded that the marked increase in GFR in volume expanded young rats is mainly due to increased renal plasma flow.     

The effect of intraarterial infusion of prostacyclin on the tubuloglomerular feedback control in the rat

Effects of intraarterial prostacyclin (PGI2) infusions on interstitial hydrostatic and oncotic pressures and on the tubuloglomerular feedback (TGF) control of glomerular filtration rate (GFR) were studied in rat kidneys. The hilar lymph flow rate was used as a measure of interstitial hydrostatic pressure and the lymph protein concentration was used for interstitial oncotic pressure estimation. In the micropuncture experiments the stop-flow pressure technique was employed for determining the TGF characteristics, i.e. stop-flow pressure (PSF), maximal reduction of PSF (delta PSF) and turning point (TP), defined as the end-proximal flow rate at which 50% of delta PSF was obtained. Non-hypotensive doses of PGI2 (50 to 100 ng X kg-1 B.W. X min-1) infused in 30 min evoked an increase in urine and lymph flow rates and a decrease in lymph protein concentration, but did not affect GFR. delta PSF was reduced (9.9 +/- 1.0 mmHg versus 4.7 +/- 2.2 mmHg) and TP increased (22 +/- 2 nl/min versus 34 +/- 2 nl/min), but the PSF was unaffected. These changes were seen during the infusion period and during the immediate post-infusion control period of 30 min. Our data indicate that non-hypotensive doses of PGI2 in some way can affect the renal interstitial pressure and the TGF control system.