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Biomedical subjects

R Greger

Publications and source records attributed to R Greger.

At least 163 records · Page 9Linked to original sources
PubMed1982

Carbonic anhydrase independent bicarbonate reabsorption.

The present study was designed to define the prerequisites of carbonic anhydrase independent bicarbonate reabsorption. In free flow experiments during systemic application of carbonic anhydrase inhibitor benzolamide (50 mg/kg B. W.) bicarbonate recovery in % of filtered load was found to be 74 +/- 8% in late proximal convoluted tubules, 39 +/- 6% in distal convoluted tubules and 32 +/- 4% in urine, indicating that most of carbonic anhydrase independent bicarbonate reabsorption occurs in tubule segments prior to distal convoluted tubules. In vivo continuous microperfusion experiments in proximal convoluted tubules demonstrated that luminal benzolamide (0.5 mmol/l) virtually abolishes net bicarbonate fluxes, when bicarbonate concentration in the luminal perfusate (25 mmol/l) is close to peritubular plasma concentration (24.4 mmol/l). In contrast, a significant downhill reabsorptive flux occurs, when perfusate bicarbonate concentration is 75 mmol/l and a significant downhill secretory flux is observed, when the perfusate is initially free of bicarbonate. The corresponding apparent permeabilities are 1.0 +/- 0.1 X 10(-6) cm2/s for influx and 1.6 +/- 0.4 X 10(-6) cm2/s for efflux of bicarbonate. Clearance studies reveal that carbonic anhydrase dependent and independent bicarbonate reabsorption are not saturable but depend on the rate of volume reabsorption in the kidney. In conclusion, passive movements of bicarbonate do occur in proximal convoluted tubules and most likely contribute to carbonic anhydrase independent bicarbonate reabsorption.

Absorption↗
PubMed1982

Membrane transport in the proximal tubule and thick ascending limb of Henle's loop: mechanisms and their alterations.

Over the past few years, our knowledge on renal tubular transport mechanisms has increased considerably. Due to new technical developments, it is now possible to understand in part transepithelial transport and its pathological and pharmacological alterations at the level of the cell membranes. Different membrane transport mechanisms are discussed in this article, whereby sodium coupled solute transport in the proximal tubule and sodium chloride transport in the thick ascending limb of Henle's loop are taken as examples. It is indicated that an altered function of the kidney can often be equated with an alteration of the membrane transport.

Animals↗
PubMed1982

A cytotoxin of Pseudomonas aeruginosa acts directly on the cortical thick ascending limb of Henle's loop of rabbit kidney.

The present study examines directly the effect of a cytotoxin of Pseudomonas aeruginosa on the in vitro perfused rabbit cortical thick ascending limb of the loop of Henle (cTAL). 25 cTAL segments were perfused at high rate. The open circuit transepithelial electrical PD (PDte) and the specific electrical transepithelial resistance (Rt) were recorded continuously. From PDte/Rt the equivalent short circuit current (Isc) was calculated. The Isc was 214 +/- 30 mu A.cm-2 under control conditions, and decreased significantly to 74 +/- 34 mu A.cm-2 60 s after the addition of toxin (2 mg.1(-1)) to the lumen perfusate. Microscopic observation and photographs taken at that time clearly indicated swelling of the cTAL cells. Thereafter inhibition of active transport proceeded further, Rt fell progressively, and cells started to desquamate from the basement membrane. This effect of the toxin was dose dependent, and was half maximal at approximately 1.2 mg.1(-1). From the bath side the effect was less marked and higher doses of toxin had to be used (half maximal effect at 5 mg.1(-1)). We conclude that this toxin of Pseudomonas aeruginosa exerts its toxic effect on the cTAL segment by increasing primarily the permeability of the lumen membrane.

Animals↗
PubMed1982

The effect of respiratory and metabolic acid-base changes on ionized calcium concentration: in vivo and in vitro experiments in man and rat.

Correlation of ionized calcium concentration, [Ca2+] and blood pH has long been recognized. So far no distinction of the acid-base changes, i.e. respiratory changes or metabolic changes seemed necessary. The present study, with the use of a recently developed system for in vivo analysis of [Ca2+], and with in vitro experiments reinvestigates this question. In a first series respiratory and metabolic changes were induced in rats. Changes of [Ca2+] (delta [Ca2+]) and of plasma pH (delta pH) were recorded continuously in vivo, plasma bicarbonate, [HCO-3] was measured in vitro. In a second series respiratory and metabolic changes were induced in sixteen volunteers and, separately, in vitro in plasma and modified Ringer solution, and the same parameters were determined. In all experiments delta [Ca2+] correlates negatively with delta pH. However, the correlation in respiratory changes was significantly less as compared to that in metabolic changes. As expected, delta [HCO-3] correlates positively with pH in metabolic and negatively in respiratory changes. We conclude from these experiments that in metabolic changes the effects of calcium-albumin interaction and calcium complexation with bicarbonate are additive, whereas both effects oppose each other in respiratory changes. This might explain the blunted effect of pH changes on [Ca2+] in respiratory changes.

Acidosis↗
PubMed1981

A modified system for in vitro perfusion of isolated renal tubules.

A modified system for the in vitro perfusion of isolated tubule segments is presented. The system consists of four holders each of which carries an acrylic cylinder. The acrylic cylinders are used to fix the glass pipettes in a concentric position. The four holders are mounted onto a support consisting of two holding pieces and three steel rods. Three of the holders contain ball-races so that they can slide on the rods with high accuracy and little friction. The holders to which the sylgard pipette and the perfusion pipette are attached are moved by electric motors. Compared with the classical V-track system this modification has the advantage of higher precision. Once the different pipettes are centered, concentricity is maintained even when the pipettes are moved forward or backward. Thus, this equipment facilitates the cannulation of tubules and increases the number of successful experiments.

Animals↗
PubMed1981

Presence of luminal K+, a prerequisite for active NaCl transport in the cortical thick ascending limb of Henle's loop of rabbit kidney.

Previous data from our laboratory have shown that active transport in the cortical thick ascending limb of Henle's loop (cTAL), as measured by the short circuit current (Lsc, microA X cm-2), requires the presence of Na+ and Cl-. The data were compatible with the model of secondarily active Cl- reabsorption involving the cotransport of Na+ and Cl- across the luminal membrane. The data suggested, furthermore, that 1 Na+ and 2 Cl- interact with the luminal carrier. In the present study it was tested whether this reabsorptive mechanism also requires the presence of luminal K+. Isolated cTAL segments (n = 40) were perfused at high flow rates with a modified Ringer's solution. Removal of K+ from the lumen reduced Isc significantly from 215 to 133 microA X cm-2. Addition of Ba2+ (10(-3) mol X 1(-1)) which blocks the K+ conductance of the luminal, membrane, to the K+-containing lumen perfusate decreased Isc significantly from 234 to 141 microA X cm-2. Combination of both manoeuvres: perfusion with a K+-free and Ba2+-containing solution almost abolished Isc from a control of 237 to 56 microA X cm-2. The results are compatible with the view that in rabbit cTAL the luminal carrier interacts with all 3 ions, possibly 1 Na+, 2 Cl-, and 1 K+. K+ recycles across the luminal membrane through its conductive pathway.

Animals↗
PubMed1981

Inefficacy of bicarbonate infusions on the course of postischaemic acute renal failure in the rat.

Since bicarbonate has been reported to elicit fast recovery from acute renal failure in man, clearance studies were performed to compare the effects of sodium bicarbonate and saline infusion on renal function in postischaemic renal failure in the rat. In a first set of experiments the left kidney and in a second both kidneys were clamped for a period of 45 min and renal function monitored up to 210 min after release of the clamp. Glomerular filtration rate (ml/min) decreased following clamping from (mean values +/- SEM) 1.33 +/- 0.09 to 0.12 +/- 0.02 (saline) or 1.43 +/- 0.1 to 0.08 +/- 0.01 (bicarbonate) in the unilaterally clamped kidney and from 2.94 +/- 0.20 to 0.41 +/- 0.10 (saline) or 2.81 +/- 0.17 to 0.22 +/- 0.03 (bicarbonate) when both kidneys were clamped. Fractional excretion of water and sodium increased to a similar extent in saline and bicarbonate treated animals. Plasma potassium decreased (from 3.37 +/- 0.10 to 2.95 +/- 0.07 [unilaterally clamped kidneys] or from 5.2 +/- 0.4 to 4.4 +/- 0.2 [bilaterally clamped kidneys]) in bicarbonate treated but remained constant in saline treated animals, an effect not related to altered renal potassium excretion. In conclusion, no evidence was found that bicarbonate improves renal function in postischaemic renal failure.

Acute Kidney Injury↗
PubMed1980

[Additive phosphaturic action of parathyrin and calcitonin (author's transl)].

Parathyrin and calcitonin exert their effects on phosphate metabolism by influencing the functions of at least three organ systems, i. e. bone, gut and kidneys. To study the renal effects of these hormones under exclusion of systemic effects microinfusion studies were performed in anesthetised rats. After thyroparathyroidectomy radioactively labelled phosphate containing solutions were microinfused into single proximal convoluted tubules. The tracer recovery in the urine allowed calculation of phosphate reabsorption in the nephron segments beyond the micropuncture site. After a control period of 6 minutes the hormones were superfused to the nephron surface and tracer recovery measured during the following 36 minutes. Within few minutes both, parathyrin and calcitonin, clearly reduced phosphate reabsorption. Infusions of supramaximal doses of either hormone abolished the local action of this hormone but did not influence the effect of the other. Thus the phosphaturic actions of parathyrin and calcitonin are additive, indicating that the hormones involve different mechanisms and/or nephron sites.

Animals↗
PubMed1980

Evidence for a bicarbonate leak in the proximal tubule of the rat kidney.

To elucidate the mechanism responsible for the establishment of steady state pH at zero net flux (pH infinity) in proximal convoluted tubules, luminal pH was recorded continuously with antimony microelectrodes under three experimental conditions. First: luminal pH in stationary droplets was allowed to reach pH infinity (6.76 +/- 0.07) and then carbonic anhydrase inhibitor benzolamide (3 x 10(-3) mol/l) was superfused on the kidney surface. Following application of benzolamide, luminal pH decreased within seconds (delta pH = -0.27 +/- 0.03 SEM). Second: tubule segments were perfused continuously with MES-buffer containing solution set to a pH of 6.1. Some 1--2 mm distal to the perfusion pipette luminal pH was recorded and was 6.5 +/- 0.04. After superfusion of benzolamide (3 x 10(-3) mol/l) pH decreased (delta pH = -0.15 +/- 0.03). Third: pH in stationary droplets was again allowed to reach PH infinity (6.69 +/- 0.01) and bicarbonate and CO2- free solution (5 mmol/l phosphate set to a pH of 7.4) was microinfused into the adjacent peritubular capillary. Luminal pH again decreased almost immediately (delta pH = -0.23 +/- 0.02). The data are interpreted as evidence for a bicarbonate leak. In a fourth series of experiments, segments of proximal tubules were perfused under benzolamide (0.4 x 10(-6) mol/min) with solutions initially free of bicarbonate or other buffers. In the collected fluid, bicarbonate was determined by a micro-Astrup method. A significant increase of luminal bicarbonate concentration (r = 0.88) indicates a permeability of 0.98 +/- 0.14 x 10(-6) cm2/s of the tubular wall for bicarbonate. Since bicarbonate eventually increases more than 3-fold the equilibrium concentration, collected bicarbonate could not have been formed by H2CO3 or CO2. Bicarbonate enters the luminal fluid and reacts with secreted hydrogen ions to forms carbonic acid. It, therefore, buffers secreted hydrogen ions and increases luminal pH at or below steady state. Inhibition of carbonic anhydrase and lowering of peritubular bicarbonate thus lower pH infinity.

Animals↗
PubMed1980

Continuous in vivo measurement of plasma ionized calcium.

A new system for continuous in vivo measurement of ionized calcium in blood is presented. The system consists of a small chamber (400 microliter) which is thermostatized at 37 degrees C and contains a glass electrode for pH measurement and a calcium selective electrode. The chamber is mounted in an arteriovenous shunt between the femoral artery and femoral vein of heparinized (approximately 1IU/min.kg B.W.) rats. The perfusion of approximately 500 microliter/min is driven by blood pressure. The system is tested in rats undergoing acute thyroparathyroidectomy and phosphate infusion. Due to this procedure ionized calcium falls from 0.9 mmol/l (total calcium 2.0 mmol/l) to 0.35 mmol/l (total calcium 1.2 mmol/l) after 5 hours. Tetany then occurs in all animals. The system presented simplifies the measurement of ionized calcium and has the advantages of immediate and continuous recording. It is especially apt for small animals in which repeated measurements with standard techniques involve large blood losses.

Animals↗