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K Aukland

Publications and source records attributed to K Aukland.

At least 19 recordsLinked to original sources
PubMed1995

Autoregulation of zonal glomerular filtration rate and renal blood flow in spontaneously hypertensive rats.

Autoregulation of total and zonal glomerular filtration rate (GFR) in outer, middle and inner cortex was estimated in spontaneously hypertensive rats (SHR), from the tubular uptake of 125I-labeled aprotinin (125I-Ap), injected at control renal arterial pressure (RAP), and 131I-Ap, injected at reduced RAP in left kidney. Normotensive Wistar-Kyoto (WKY) rats were used as controls. Renal blood flow (RBF) autoregulation was reset to higher pressure levels in SHR. When RAP was lowered close to the lower pressure limit of RBF autoregulation, total GFR was reduced to 89.5 +/- 3.1 and 88.1 +/- 3.3% of control in 10- and 40-wk WKY and to 87.7 +/- 2.3 and 88.0 +/- 2.2% in 10- and 40-wk SHR. In WKY, the fall of GFR in the three cortical layers was not different during RAP reduction. In 10- and 40-wk-old SHR, however, GFR fell significantly less in inner than in middle and outer cortex (P < 0.05). We conclude that autoregulation of GFR is most efficient in the inner cortex of SHR. In all animals, GFR was less well autoregulated than RBF.

Animals↗
PubMed1994

Repeatable measurement of local and zonal GFR in the rat kidney with aprotinin.

The basic polypeptide aprotinin (Ap), mol. wt 6513, is freely filtered in glomeruli and completely reabsorbed by the proximal tubules. Cellular processing is slow with return to plasma of breakdown products beginning after 20-30 min. When corrected for Gibbs-Donnan distribution of Ap between glomerular filtrate and plasma (i.e. 0.65 at a plasma protein concentration of 50 mg ml-1), the renal clearance of [125I]Ap, estimated as the ratio of kidney uptake and integrated non-protein bound plasma 125I concentration, equals that of [51Cr]EDTA (urine + kidney content). Zonal GFR per gram tissue was obtained from uptake in three to six samples from outer and inner cortex (OC, IC) and the cortico-medullary border zone, 5-30 min after i.v. injection in rats. Control GFR in OC was 2.05 (SD 0.39) ml g-1 min-1 and the IC/OC ratio 0.66 (SD 0.14). Repeated local clearances (CI and CII) were obtained by injecting a second tracer (i.e. [131I]Ap) 15 min after the first injection (i.e. [125I]Ap), which by then had a low plasma concentration. The kidneys were removed at 30 min, frozen and dissected. During control conditions CII/CI averaged 1.06 in OC and IC, and the coefficient of variation (CV) between CII/CI ratios of individual tissue samples was 2% in both zones. Lowering left renal arterial pressure before the second injection reduced GFR proportionally in both zones (34 and 37%) with a CV of intersample CII/CI ratios of 5%. We conclude that the method allows precise and repeatable measurements of local and zonal GFR.

Animals↗
PubMed1994

Glomerular filtration and tubular absorption of the basic polypeptide aprotinin.

The basic polypeptide aprotinin (Ap), mol. wt 6500, pI 10.5, is filtered in the glomeruli, virtually completely taken up by the proximal tubular cells and retained there for many hours. This process was studied in rats by determining the renal plasma clearance (CAp) as the amount of [125I]Ap accumulated in the kidney plus that excreted in the urine per unit of time divided by the integrated plasma concentration. In periods lasting 4-20 min after i.v. bolus injection or infusion to constant plasma concentration, CAp was 65% of glomerular filtration rate (GFR) estimated as kidney plus urinary clearance of [51Cr]EDTA (Ccr-EDTA). Less than 0.8% of the filtered Ap appeared in the urine. CAp varied inversely with plasma protein concentration in mg ml-1: CAp/Ccr-EDTA = 0.98-0.0058 x Ppr, corresponding to a glomerular Gibbs-Donnan distribution for a net molecular charge of +6, in agreement with the amino acid composition of Ap. CAp (kidney + urinary) was not altered by inhibiting tubular uptake of [125I]Ap by maleate or by exceeding the uptake capacity with large doses of unlabelled Ap. Neutralized Ap (malonylated) did not accumulate in the kidney, but showed a urinary clearance indistinguishable from that of [51Cr]EDTA. Both CAp and Ccr-EDTA were reduced to 0.04 ml min-1 when glomerular filtration pressure was lowered by ureteral stasis and increased Ppr (80-90 mg ml-1). These findings indicate: (1) no steric or charge restriction to filtration of Ap in the glomerular membrane, (2) the Gibbs-Donnan equilibrium should be considered when estimating glomerular sieving of charged polypeptides in intact animals (3) charge dependent tubular uptake, (4) little or no transtubular transport of intact Ap, (5) no appreciable tubular uptake of Ap from the peritubular side and (6) local renal accumulation of Ap in a period of up to 20 min may be used to estimate local glomerular filtration and/or local proximal tubular reabsorption rates. Model analysis based on the appearance of 125I in plasma, the time course of renal Ap content, and literature data on subcellular Ap distribution are consistent with two populations of endosomes, transporting Ap at widely different rates from the proximal tubular brush border to the lysosomes where breakdown occurs at a high rate.

Absorption↗
PubMed1992

Myogenic vasoconstriction in the rat kidney elicited by reducing perirenal pressure.

Autoregulation of renal blood flow is generally believed to result from tubuloglomerular feedback and/or a vascular myogenic mechanism, but there is no consensus on the relative importance of these mechanisms. We designed an experiment in which tubuloglomerular feedback would tend to oppose a myogenic response: the denervated kidney in situ was enclosed in an airtight chamber and exposed to a 35 mmHg subatmospheric pressure for 1 to 10 minutes. Renal blood flow recorded by an electromagnetic flowmeter fell by 33% in the course of a few seconds. Renal venous concentration of inulin showed no consistent change, indicating similar reduction in glomerular filtration rate. Since urine flow also fell, it is likely that the tubular flow rate was reduced. The kidney volume expanded by 10-20%, and subcapsular interstitial fluid pressure was reduced from 6.8 to -8.6 mmHg. Arterial pressure remained unchanged, while renal venous pressure inside the chamber fell from 9.4 to 5.8 mmHg. Normalization of perirenal pressure gave rapid normalization of all parameters. Elevation of ureteral pressure attenuated or even prevented the renal blood flow reduction. Renal decapsulation or sympathetic blockade by phentolamine, or infusion of furosemide or 0.9% NaCl to inactivate tubuloglomerular feedback, did not prevent the renal blood flow reduction. We interpret the results to indicate that myogenic vasoconstriction greatly overpowered TGF and even surpassed the constriction predicted by a mathematical model based on maintenance of the preglomerular wall tension as estimated from transmural pressure.

Animals↗
PubMed1991

Oedema-preventing mechanisms in a low-compliant tissue: studies on the rat tail.

The long-term effect of elevated tail venous pressure (Pv) on interstitial fluid pressure (Pi) and colloid osmotic pressure (COPi) was studied in rats. Measurements were performed on different rats after 1-5 days of congestion, and on a sham operated control group. Two different degrees of venous stasis were obtained by means of graded ligation of tail veins and skin. Moderate degree of ligation (group 1) caused no visual oedema. More extensive ligation (group 2) gave marked oedema already on day 1 and further progression and exudation from the skin during the following 3 days. Tail venous pressure was measured by micropuncture and interstitial fluid pressure by the wick-in-needle technique. Interstitial fluid was sampled by a dry wick method, and colloid osmotic pressure was measured with a membrane osmometer. In group 1, Pv had increased from 6.5 to 21.5 mmHg on day 1, and thereafter remained unchanged. Interstitial fluid pressure increased from 3.4 to 16.9 mmHg after ligation and to 19.2 mmHg on day 1. Colloid osmotic pressure fell from 11.7 to 5.8 mmHg. From day 1, both interstitial fluid pressure and colloid osmotic pressure remained largely unchanged. In group 2 rats, tail venous pressure increased to 33.0 and 36.3 mmHg on day 1 and 2 and then fell towards control level during the following 3 days. Interstitial fluid pressure increased to 22.9 and 31.4 mmHg before a rapid decline towards control level. Colloid osmotic pressure was reduced from 11.7 to 5.6 mmHg. We conclude that hydrostatic counterpressure may provide an oedema-preventing effect of up to about 15 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effect of longstanding venous stasis and hypoproteinaemia on lymph flow in the rat tail.

This study was performed to provide information on the determinants of lymph flow by comparing the effect of venous stasis and hypoproteinaemia in the rat tail. This low-compliant tissue was chosen in an attempt to induce preferential changes in interstitial pressure or volume. The removal rate (kAlb) of 125I-labelled human serum albumin (I-HSA) injected subcutaneously was monitored with external gamma-counting equipment and used as a measure of lymph flow. Interstitial fluid hydrostatic pressure (Pi) was measured with wick-in-needle technique, and interstitial fluid was collected post mortem by dry wicks. Colloid osmotic pressure of plasma (COPp) and wick fluid (COPi) was measured with a colloid osmometer. In a separate group of experiments, 51Cr-EDTA and [125I]HSA were used to measure the interstitial fluid volume. Venous stasis, induced by bilateral ligation of the external tail veins, increased interstitial fluid hydrostatic pressure from 1.7 to 16 mmHg and kAlb from 0.030 to 0.063 h-1, whereas tail circumference was nearly constant. Interstitial volume averaged 1.17 ml/g dry weight in control animals and 1.27 ml/g during increased venous pressure. Daily injections of aminonucleoside in salt-loaded rats (0.3% NaCl as drinking water) reduced colloid osmotic pressure of plasma from 19.1 to 8.5 mmHg and of wick fluid from 11.2 to 2.9 mmHg, while interstitial fluid hydrostatic pressure increased to 5.2 mmHg. The removal rate of 125I-labelled human serum albumin increased to 0.113 h-1, compared to 0.051 h-1 in salt-loaded controls. The interstitial volume showed a marked increase in salt-loaded hypoproteinaemic rats, 1.75 ml/g dry weight, compared to 1.30 ml/g in salt-loaded controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

A multinephron model of renal blood flow autoregulation by tubuloglomerular feedback and myogenic response.

Tubuloglomerular feedback implies that a primary increase in arterial pressure, renal blood flow, glomerular filtration and increased flow rate in the distal tubule increase preglomerular resistance and thereby counteract the primary rise in glomerular filtration rate and renal blood flow. Tubuloglomerular feedback has therefore been assumed to play a role in renal autoregulation, i.e., the constancy of renal blood flow and glomerular filtration at varying arterial pressure. In evaluating this hypothesis, the numerous tubular and vascular mechanisms involved have called for mathematical models. Based on a single nephron model we have previously concluded that tubuloglomerular feedback can account for only a small part of blood flow autoregulation. We now present a more realistic multinephron model, consisting of one interlobular artery with an arbitrary number of evenly spaced afferent arterioles. Feedback from the distal tubule was simulated by letting glomerular blood flow exert a positive feedback on preglomerular resistance, in each case requiring compatibility with experimental open-loop responses in the most superficial nephron. The coupling together of 10 nephrons per se impairs autoregulation of renal blood flow compared to that of a single nephron model, but this effect is more than outweighed by greater control resistance in deep arterioles. Some further improvement was obtained by letting the contractile response spread from each afferent arteriole to the nearest interlobular artery segment. Even better autoregulation was provided by spreading of full strength contraction also to the nearest upstream or downstream afferent arteriole, and spread to both caused a renal blood flow autoregulation approaching experimental observations. However, when the spread effect was reduced to 25% of that in each stimulated afferent arteriole, more compatible with recent experimental observations, the autoregulation was greatly impaired. Some additional mechanism seems necessary, and we found that combined myogenic response in interlobular artery and tubuloglomerular feedback regulation of afferent arterioles can mimic experimental pressure-flow curves.

Animals↗
PubMed1991

Distribution volumes and macromolecular mobility in rat tail tendon interstitium.

This study explores a centrifugation technique for estimating interstitial fluid composition and macromolecular transport. Rat tail tendon supported by a nylon net was subjected to three consecutive 15-min centrifugations at 3,000, 6,000, and 14,000 revolutions per minute (rpm) or 3, 10, and 20 min at 6,000 rpm. Colloid osmotic pressure (COP) and concentrations of albumin, total protein, and hyaluronan in subsequent centrifugate fell as exponential functions of accumulated centrifuged volume, reaching 10-30% of initial level at an accumulated volume corresponding to 8% of tendon volume. Intercepts for zero centrifugation were 11 mmHg (COP), 22 mg/ml (albumin), and 39 mg/ml (total protein), probably reflecting concentrations in protein-accessible interstitial volume. Corresponding serum values were 19 mmHg, 34 mg/ml, and 63 mg/ml. Tendon distribution spaces were 0.62 (H2O), 0.57 (51Cr-labeled-EDTA), and 0.22 ml/g wet wt (albumin). The progressive fall in centrifugate concentrations probably reflects increasing resistance to macromolecular transport, with a sieving coefficient for albumin falling from 1 to 0.35, or increasing contribution of fluid from protein-excluded space. The effect was reversed by rehydration, which caused increased concentrations in centrifugate. Low hyaluronan concentrations in centrifugate (0.25 mg/ml) compared with that of whole tendon (0.4 mg/g wet wt) reflect either a large "bound" fraction in tissue or marked sieving of hyaluronan in normohydration.

Animals↗
PubMed1990

Pathophysiological aspects of edema formation in diabetic nephropathy.

The present study was undertaken to evaluate some pathophysiological mechanisms of edema formation in diabetic nephropathy. Sixty-three subjects were investigated: 9 normal subjects (I), 9 normoalbuminuric Type 1 (insulin-dependent) diabetic patients (II), 15 microalbuminuric Type 1 diabetic patients (III), 16 Type 1 diabetic patients with nephropathy without edema (IV), and 14 Type 1 diabetic patients with nephropathy and edema (V). Plasma volume (125I-albumin), glomerular filtration rate and extracellular fluid volume (51Cr-EDTA) were measured. Colloid osmotic pressure and albumin concentration were measured in plasma and in subcutaneous interstitial fluid (suction blister technique). The ratio between plasma volume and interstitial fluid volume was reduced in patients with edema compared with group 1 (P less than 0.05). The interstitial colloid osmotic pressure (mm Hg) was significantly reduced (P less than 0.05) in group V compared with the other groups (V: 4.3 +/- 1.1, I: 7.9 +/- 1.7, II: 7.5 +/- 1.8, III: 6.6 +/- 1.5, IV: 6.6 +/- 1.1), but the transcapillary colloid osmotic gradient in patients with edema was comparable with the remaining subjects. The ratio between interstitial and plasma albumin concentration was significantly reduced in group V compared with groups I and II (V: 0.31 +/- 0.1, I: 0.43 +/- 0.06, II: 0.44 +/- 0.06; P less than 0.01; III: 0.41 +/- 0.07, IV: 0.41 +/- 0.08). This reduction was mainly due to enhanced lymph flow. The wash-down of subcutaneous interstitial protein indicated increased capillary filtration, but at the same time limited the increase in net filtration pressure and thereby prevented progressive edema formation in diabetic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Myogenic mechanisms in the kidney.

Myogenic mechanisms in the kidney are part of the autoregulation mechanism which maintains a constant renal blood flow at varying arterial pressure. Concomitant autoregulation of glomerular pressure and filtration indicates regulation of preglomerular resistance. Model and experimental studies were performed to evaluate two mechanisms in the kidney, myogenic response and tubuloglomerular feedback. A mathematical model showed good autoregulation through a myogenic response, aimed at maintaining a constant wall tension in each segment of the preglomerular vessels. Tubuloglomerular feedback gave rather poor autoregulation. The myogenic mechanism showed 'descending' resistance changes, starting in the larger arteries, and successively affecting downstream preglomerular vessels at increasing arterial pressures. This finding was supported by micropuncture measurements of pressure in the terminal interlobular arteries. Evidence that the mechanism was myogenic was obtained by exposing the kidney to a subatmospheric pressure of 40 mmHg; this led to an immediate increase in renal resistance, which could not be prevented by denervation or various blocking agents.

Animals↗
PubMed1988

Measurement of colloid osmotic pressure in submicrolitre samples.

A colloid osmometer for submicrolitre samples was constructed from solid polymethylmetacrylate and acrylnitrilmethylmetacrylate blocks, exposing a 0.85 mm diameter area of a Diaflo PM-30 ultrafiltration membrane. The unknown sample, contained in a 1-microliter glass micropipette, was applied to the membrane by suction, providing minimal exposure to air. The lower limit for successful application was 0.1-0.2 microliter. The accuracy of colloid osmotic pressure (COP) measurement depends strongly on the effective compliance of the pressure transducer. We tested three different systems: (i) A Hewlett-Packard 1280 'medical' transducer gave acceptable measurements on 1-microliter samples. In smaller samples (0.1-0.5 microliter) COP was underestimated, especially at COP greater than 10 mmHg. The equilibration time was 10-30 min. (ii) As (i), but with air pressure applied to the sample by a servoregulated pump, minimizing fluid transport through the membrane. Accurate measurements on 0.2-microliter samples were obtained in the course of 2-3 min, but the system required special instrumentation and some operating experience. (iii) An 'industrial' transducer, SensoNor AE-88o, with very low compliance, gave accurate measurements in the course of 1-3 min on samples as small as 0.1-0.2 microliter and COP up to 37 mmHg. We recommend system (iii) for samples smaller than 1 microliter.

Colloids↗
PubMed1988

Colloid osmotic pressure of interstitial fluid in rat subcutis and skeletal muscle: comparison of various wick sampling techniques.

Interstitial fluid for measurement of colloid osmotic pressure (COPi) was collected from rat subcutis and skeletal muscle with three wick methods; saline-soaked wicks implanted in vivo, titration with wicks preloaded with serial dilutions of rat plasma implanted postmortem (crossover method) and dry wicks implanted in vivo and post-mortem. When compared in 12 rats, the mean subcutaneous COPi of 14.2 and 13.3 mmHg as estimated with the crossover method and dry wick method, respectively, both exceeded the 10.7 mmHg obtained in saline-soaked wicks implanted for 60 min. Colloid osmotic pressure (COP) in fluid from dry wicks implanted subcutaneously was slightly lower than in plasma 5 min after implantation in vivo, then fell gradually, but remained stable the last 30 min of the 60 min in vivo implantation period and the first 30 min post-mortem, when again starting to rise. COP in fluid isolated from dry wicks implanted in muscle post-mortem approached or even exceeded that of plasma, suggesting leakage of intracellular proteins to wick fluid. Electrophoresis of dry wick fluid from subcutis showed a pattern similar to that of plasma, while protein fractions not present in plasma were observed in muscle wick fluid. For measurement of COPi we recommend the use of dry wicks implanted post mortem for subcutis and saline-soaked or dry wicks implanted in vivo for 90-120 min for skeletal muscle.

Animals↗
PubMed1987

Interlobular arterial resistance: influence of renal arterial pressure and angiotensin II.

Pressure in the distal third of the interlobular arteries (Pila) was measured in anesthetized rats by micropuncture through corticotomy. Control Pila was 83.9 (SD 11.9) mm Hg at a renal arterial pressure (RAP) of 113.1 (SD 12.8) mm Hg. Reduction of RAP by 20 mm Hg caused no consistent change of total renal blood flow (RBF) or Pila. Relative interlobular arterial resistance, Rila = (RAP - Pila)/RBF, fell by 40 to 50%, and then remained practically unchanged at further reduction of RAP. Blood flow measured by radiolabeled microspheres (10.7 micron) showed similar values in intact cortex and in the tissue beneath the corticotomy, both varying in proportion to RBF. Intravenous infusion of angiotensin II (AII) 40 to 90 ng/min reduced RBF by 29% and increased RAP by 19 mm Hg. Pila rose by only 8 mm Hg and Rila increased to 209% of control. Reduction of RAP to control level during continued AII infusion did not change RBF, while Rila fell to 131% of control. We conclude that: dilatation and constriction of the interlobular arteries contribute importantly to autoregulation of outer cortical blood flow, probably through a myogenic mechanism (Bayliss); the constriction of interlobular arteries elicited by i.v. AII reflects mainly an autoregulatory response to increased arterial pressure, and to a smaller extent, a direct constrictor effect of AII.

Angiotensin II↗
PubMed1987

Measurement of colloid osmotic pressure in body fluids: errors caused by preheparinized glass capillaries and by CO2 loss.

The effect on colloid osmotic pressure (COP) of heparinizing body fluids was estimated with a low compliant osmometer, using Diaflo PM-30 or PM-10 membranes (Amicon, Lexington, Mass., USA). It was found that collecting and storing samples in preheparinized glass capillaries may increase COP by up to 4.0 mmHg. Measurements on heparin and protein solutions, separately and mixed, show that these macromolecules have a mutually potentiating effect on COP, probably by excluding part of the water as distribution space for the other molecular species. While this 'heparin error' varies among various types and batches of capillaries (Vitrex, Modulohm I/S), the content of heparin in some batches appears to be two to three times greater than the declared minimum. Alternatively, the excess COP may result from addition of other water-soluble macromolecules in the heparinization process. Even if some batches do not give appreciable error, we recommend to avoid preheparinized capillaries for measurement of COP. Both defibrination, and the amount of heparin needed to anticoagulate macro blood samples, have insignificant effect on COP. Loss of CO2 by diffusion from separated plasma may increase pH towards 9.5. Concomitantly, COP increased by 2.1 mmHg per pH-unit. If plasma or serum samples are capped within some minutes after separation, they may be stored for weeks at 4 degrees C in polyethylene tubes without appreciable change of COP.

Animals↗
PubMed1987

Measurement of interstitial fluid pressure in dogs: evaluation of methods.

Interstitial fluid pressure (IFP) was measured with two acute (micropipettes and wick-in-needle) and two chronic methods (perforated and porous capsules) in dog skin/subcutis. In control conditions all techniques gave similar mean pressures, approximately -2 mmHg. Overhydration induced by intravenous Ringer infusion, 10% of body wt, caused two to three times greater increase in pressure recorded with chronic than with acute methods but 2 h after the end of the infusion all methods gave similar pressures. An almost opposite pattern was observed during dehydration induced by peritoneal dialysis with hypertonic glucose. The fall in pressure recorded with the perforated capsule exceeded that of the porous capsule, both exceeding the pressure reduction measured with the acute methods by a factor of 2-5. The difference between pressures measured with both acute methods and the perforated capsule increased in the 90 min following dialysis. Acute overhydration or dehydration as well as aspiration from or infusion into perforated capsules caused a pressure gradient between lumen, capsule wall, and surrounding skin. We propose that the transient pressure differences recorded by acute vs. chronic methods during changes in hydration result from different physical properties of the capsule lining compared with that of the surrounding skin, in addition to a possible osmometer effect of the capsule lining.

Animals↗
PubMed1987

Renal autoregulation: models combining tubuloglomerular feedback and myogenic response.

As shown previously, autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR) at varying arterial pressure may result from a myogenic response (MR) acting to maintain wall tension in each preglomerular vessel segment. We now combine MR with tubuloglomerular feedback (TGF) responding to distal tubular flow rate. The model consists of preglomerular and postglomerular resistances, glomerular filtration, and a tubular system. TGF acting on preglomerular resistance with parameters that mimic responses to single nephron distal tubular flow rate in rats and dogs failed to account for the autoregulation of RBF and GFR observed experimentally. Good autoregulation was obtained by adding preglomerular MR. In this combination, TGF is activated mainly in the lower range of autoregulation. Addition of mechanisms that increase postglomerular resistance or increase the glomerular filtration coefficient at reduced arterial pressure impairs RBF autoregulation, whereas GFR autoregulation is only slightly improved. TGF regulation of pre- and postglomerular resistance in the same direction seems compatible with good autoregulation only when combined with a preglomerular myogenic mechanism.

Animals↗