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Biomedical subjects

A E Persson

Publications and source records attributed to A E Persson.

At least 109 records · Page 6Linked to original sources
PubMed1982

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.

Acetazolamide↗
PubMed1982

Modulation of proximal tubular hydraulic conductivity by peritubular capillary oncotic pressure.

Fluid absorption from the proximal tubular lumen is probably a multifactorial process. Earlier studies from our laboratory have indicated that a transepithelial hydrostatic and oncotic pressure difference may be the driving force for as much as 30% of the reabsorbed fluid. During saline volume expansion proximal tubular reabsorption declines and the present experiments were undertaken to investigate whether this reduction could be caused by changes in the passively driven flux component. The hydraulic conductivity was therefore determined from the reabsorptive rate in split oil droplets with normal and high hydrostatic pressure gradients across the wall, at the same time as the peritubular capillary net-work was perfused with solutions containing a colloid of high or low concentration. In the reabsorption experiments the split oil droplet radius was measured and in a separate series of experiments the relationship between droplet radius and pressure was determined; this was found to be 7.3 mmHg pressure increase per 1 micrometer increase in radius. The increase in the rate of reabsorption from the droplets due to increased intraluminal hydrostatic pressure was 1.02 +/- 0.13 nl/min/mm tubular length when a solution with a high colloid concentration was perfused through the capillary net-work, compared with 0.41=0.11 nl/min/mm tubular length when a low colloid containing solution was used for perfusion. The hydraulic conductance in the proximal tubular wall at high colloid perfusion was calculated to be 0.54 nl/min.mm.mmHg while at a low capillary colloid oncotic pressure it was significantly lower 0.025 nl/min.mm.mmHg. This drop in hydraulic conductance might be one factor responsible for the decline in fluid absorption in animals exposed to saline volume expansion.

Animals↗
PubMed1982

Studies of the sensing mechanism in the tubuloglomerular feedback pathway.

Two aspects of the single nephron feedback response previously observed by us have been reexamined. The first, the effect of modifying the composition of fluid used to perfuse the loop of Henle of a single nephron, was studied in rats by comparing flow-induced changes in stop-flow pressure (PSF) with three different perfusion solutions: artificial tubule fluid (ATF); 0.3 M mannitol (M); and mannitol plus 25 to 30 mM sodium chloride (M + E). The second, triggering of the feedback response by injection of ionic current into the distal tubule, was studied in similarly prepared rats by monitoring PSF while passing current. Increasing the rate of loop of Henle perfusion with either ATF or M + E resulted in similar decreases in PSF. In contrast, with M, changes in PSF were usually transient and if persistent were smaller than the changes observed with the other two solutions. When loops of Henle were perfused with ATF at a constant rate, injection of current into the early distal tubule making the lumen more negative resulted in decreases in PSF. Currents of opposite polarity caused no change in PSF if loop flow rate was low; these currents increased PSF if the loop flow rates had previously been high. Current-induced feedback responses were obtained with micropipette electrodes filled with either potassium chloride or lithium acetate. Addition of 10(-4) M furosemide blocked the current-induced feedback responses.

Animals↗
PubMed1982

Tubuloglomerular feedback in juxtamedullary nephrons.

Hitherto, no experimental evidence for the existence of tubuloglomerular feedback regulation (TGF) in juxtamedullary nephrons has been produced. We have developed two micropuncture techniques suitable for the papilla of young rats, which make it possible to investigate TGF in deep nephrons. The first consisted of measuring the tubular flow in the descending limb of Henle (VDLH) while the ascending limb (ALH) was perfused at various rates with modified Ringer solution. The single nephron filtration rate (SNGFR) was also measured in several juxtamedullary nephrons in these perfusion studies. A second micropuncture protocol was to measure the tubular stop-flow pressure (PSF) in the descending limb of Henle upstream to a wax block. Distal to the block, Ringer was perfused at various rates through ALH. The PSF, the maximal PSF decrease (delta PSFmax), and the flow rate at which 50% of the delta PSFmax was obtained (turning point, TP) were determined. The VDLH and the SNGFR decreased during Ringer perfusion (rate of more than 7.5 nl/min) to 39 +/- 4% (N = 8) and 44 +/- 4 (N = 8) of the value at zero perfusion, respectively. Even the stop-flow technique gave evidence for TGF in juxtamedullary nephrons: The PSF decreased from 40 +/- 2 mm Hg by a delta PSFmax of 14.1 +/- 1.4 mm Hg. The TP was 8.2 +/- 0.6 nl/min. Thus, similar to earlier reports on surface nephrons, the TGF is present also in the juxtamedullary nephrons, decreasing their glomerular capillary pressure, decreasing their SNGFR, and decreasing their flow rate in the descending limb of Henle when flow rate of the ascending limb is increased. Thus, TGF exerts its effect on GFR of the whole kidney not only in surface but also in juxtamedullary nephrons.

Animals↗
PubMed1981

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 mammalian animals, could be one way by which amphibians regulate the glomerular filtration rate (GFR). To investigate whether the Amphiuma means shows any sign of a tubulo-glomerular 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 occurring 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 (Raff) and efferent (Reff) arteriolar resistances were calculated. Reff did not change, while Raff increased significantly when a feedback stimulus was applied. These experiments indicate the existence of a tubulo-glomerular feedback control which depresses the SNGFR and SFP by contracting the afferent arteriole.

Animals↗
PubMed1975

The hydraulic conductivity of the rat proximal tubular wall determined with colloidal solutions.

The hydraulic conductivity of the rat proximal tubular wall was determined using colloidal solutions perfused in short (50--200 mum) (SMP) or long (90--200 mum) (LMP) proximal tubular segments. In SMP human serum albumin (HSA) or polyvinylpyrrolidone (PVP) was added to raffinose solutions. A Lp of 0.019 nl-min-1-mm-1-mm Hg-1 was found when high colloid concentrations were used while values of 0.055--0.092 were found when low colloid concentrations were used. In other experiments, the Lp was determined by perfusing short tubular segments with pure raffinose solutions. A value of 0.015 nl-min-1-mm-1-mm Hg-1 was found. This is twice the value found when raffinose solutions were perfused through long tubular segments and it is concluded that the short microperfusion technique overestimates Lp with a factor of two. When microperfusions of long tubular segments were conducted, PVP was added to an equilibrium solution consisting of NaCl (110 mM) and raffinose (80 mM). Lp was found to be 0.018--0.021 when high colloid concentrations were used, while a value of 0.029 was found when a low colloid concentration was used. As found in both SMP and LMP a decrease in Lp's with increasing colloid concentrations indicates that a significant influence of radial concentration differences is highly probable. It is therefore suggested that the highest Lp derived when using the lowest colloid concentrations represents the best estimate. With this Lp value (0.03--0.05 nl-min-1-mm-1-mm Hg-1) and the existing transtubular hydrostatic and oncotic pressure difference it can be calculated that these passive forces might constitute the driving force for 1/3 of the fluid reabsorbed in the proximal tubule.

Animals↗
PubMed1973

Tubuloglomerular feedback. Nonlinear relation between glomerular hydrostatic pressure and loop of henle perfusion rate.

The present experiments were performed to quantify the effect of changes in distal tubular sodium delivery on glomerular flow dynamics both below and above the normal physiologic range. Glomerular capillary pressure as derived from the tubular stop flow pressure was assessed while the loop of Henle of the same nephron was perfused with varying flow rates. During Ringer perfusion no change of glomerular capillary pressure was observed when flow was increased from 0 to 13 nl/min. Further increasing flow to 27 nl/min was associated with a reduction of glomerular hydrostatic pressure by an average of 7.0+/-4.4 cm H(2)O (+/-SD). During perfusion at a rate of 43 nl/min glomerular pressure was decreased by a mean of 10.5+/-4.0 cm H(2)O. Changing the flow rate in small steps revealed that a significant reduction of capillary pressure was found when increasing the flow rate from 13 to 21 nl/min and that the maximum response was reached at 32 nl/min. No effect of perfusion rate changes on glomerular capillary pressure was observed when 300 mM mannitol was used as perfusion fluid. These results imply that a nonlinear relationship exists between end-proximal flow rate and glomerular capillary pressure. It is suggested that during deviations of distal sodium delivery into a positive direction filtration rate is intrarenally regulated probably by prevalence of afferent arteriolar constriction. During reductions of distal sodium load intrarenal regulation is either abolished or it involves proportionate resistance changes of both afferent and efferent arterioles.

Animals↗
PubMedDate not supplied

Increased tubuloglomerular feedback reactivity is associated with increased NO production in the streptozotocin-diabetic rat.

The characteristics of the tubuloglomerular feedback (TGF) mechanism were examined in streptozotocin-diabetic rats. This model is known to induce damage in the distal tubular system and thus Tamm-Horsfall protein (THP) secretion. Three groups of male Sprague-Dawley rats were studied: (A) diabetic rats with blood glucose levels (BG)<19 mmol/l, (B) with BG>/=19 mmol/l, and (C) control rats. After 50 days, the diabetic rats had higher arterial blood pressure and increased TGF reactivity (delta P(SF)) than control rats. The proximal tubular free-flow pressure (P(T)) and stop-flow pressure (P(SF)) were reduced, while the glomerular filtration was normal. This indicates that the diabetic animals of this study were severely vasoconstricted. Inhibition of renal nitric oxide synthase (NOS) resulted in a greater increase of TGF reactivity in diabetic rats than in control rats. Diabetic rats also showed increased excretion rates of albumin and THP. The excretion rate of THP was associated with P(SF) (r=-0.88, p<0.01). In conclusion, diabetes mellitus was associated with an increased blood pressure and an increased TGF reactivity, which indicates that the diabetic rats were vasoconstricted. NOS inhibition increased the reactivity of TGF to greater extent in diabetic animals than in controls, indicating that the renal vasoconstriction was compensated for by an increased NO production.

Animals↗
PubMedDate not supplied

Pelvic pressure and tubuloglomerular feedback in hydronephrosis.

From previous studies on hydronephrotic rats in our laboratory, an increased sensitivity of the tubuloglomerular feedback (TGF) mechanism was found during extracellular volume expansion (VE). In contrast, the mechanism resets to a lower sensitivity during VE in control animals. The resetting in hydronephrotic rats was reversed by blocking the thromboxane (Tx) system. The present study was performed to measure changes in pelvic pressure (Pp) in hydronephrotic kidneys during VE, and the effect of Tx inhibition on those changes. In addition, TGF was characterized during VE of hydronephrotic rats while Pp was kept at the pre-VE level. On VE, Pp increased moderately from a control value of 2.9 mm Hg to a plateau with a mean value of 6.0 mm Hg (control, 0.7 vs. 2.1 mm Hg). After Tx inhibition, Pp was increased by more than 100%, with a plateau value of 13.6 mm Hg. When Pp was normalized and fixed, the direction of resetting of TGF was normal. The results from this study indicate that the resetting of TGF is of importance to keep glomerular filtration rate low and reduce Pp in the hydronephrotic kidney. Tx and Pp are involved in the resetting of TGF.

Animals↗
PubMedDate not supplied

Effect of prostaglandin synthesis inhibition on the tubuloglomerular feedback control in the rat kidney.

It is known that intact prostaglandin synthesis is of some importance for tubuloglomerular feedback (TGF). In this study the effects of cyclooxygenase inhibition by oral fenflumizole, an imidazole derivative, on TGF in rats after acute elevation of ureteral pressure were investigated by comparison with the TGF mechanism in untreated rats. The effects of fenflumizole on the TGF mechanism were also compared with those of indomethacin injection. To characterize the TGF mechanism proximal tubular stop-flow pressure (Psf) was measured during perfusion of the loop of Henle with an artificial perfusion solution with a composition resembling that of the proximal fluid. The perfusion rate was varied from 0 to 40 nl.min-1, in steps of 2.5-5 nl.min-1, permitting measurement of the maximal pressure response delta Psf, to increased tubular perfusion, and the perfusion rate which elicited a half-maximal drop in Psf, designated the turning point (TP). Both cyclooxygenase inhibitors caused a significant increase in TP from a control value of 21 to approximately 27 nl.min-1. TP remained at this level in fenflumizole-treated rats, even after elevation of ureteral pressure, a situation in which TGF is normally not detectable. From these and earlier investigations we conclude that the prostaglandin system is of importance for a normally operating TGF control mechanism, both under normal conditions and, especially, in conditions in which resetting of TGF is observed.

Animals↗