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Biomedical subjects

R Greger

Publications and source records attributed to R Greger.

At least 145 records · Page 8Linked to original sources
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↗
PubMed1980

Renal handling of urate in healthy man in hyperuricaemia and renal insufficiency: circadian fluctuation, effect of water diuresis and of uricosuric agents.

To differentiate between extrarenal and renal causes of hyperuricaemia and gout, clearances of urate and creatinine were monitored for 3 1/2 days in fifty-two individuals (seven with a history of gout) with no gross impairment of renal function (creatinine clearance 52-137 ml/min). Dietary purine intake was kept constant. Monophasic circadian fluctuations of fractional urate excretion (= urate clearance over creatinine clearance) were observed with peak values in the afternoon, about 50% higher than during the night. Circadian fluctuations of urinary flow rate were almost identical. However, enhancement of urinary flow rate due to water diuresis had no effect on urate clearance. Despite wide variation of plasma urate concentrations among different individuals (+/- 30% SD), daily urate excretion varied little (+/- 4% SD) and did not correlate with plasma urate (r = 0.03). Thus extrarenal factors appear not to account for the occurrence of hyperuricaemia in these patients. In contrast, a clearcut negative correlation was apparent between plasma urate concentration and fractional urate clearance (r = 0.72), which could fully account for the variations of plasma urate concentration. To elucidate further the mechanism responsible for antiuricosuria in hyperuricaemic patients, the effects of the uricosuric agents benzbromarone and probenecid were tested. A clearcut correlation was apparent between control fractional urate excretion and uricosuric effect of both benzbromarone and probenecid (r = 0.83 and 0.88, respectively), suggesting that anti-uricosuria was due to defective secretion. In an additional series, the uricosuric effect of probenecid was tested in ten patients with renal insufficiency. In these patients the uricosuric effect was clearly blunted, indicating that urate reabsorption is reduced in renal insufficiency.

Adult↗
PubMed1979

Influence of calcium and ionophore 23187 on tubular phosphate reabsorption.

In previous studies it has been demonstrated that a decline of plasma calcium concentration accounts for the decrease of phosphate reabsorption in thyroparathyroidectomized (TPTX) rats undergoing phosphate loading. Microinfusion studies were performed in TPTX rats in order to discriminate between a systemic effect of calcium an a direct renal effect. Thyroparathyroidectomized animals were infused with a phosphate solution continuously. When plasma calcium concentration fell below 1.30 mmol/l, proximal convoluted tubules were microinfused with a phosphate tracer solution for 42 min. After 18 min a calcium chloride-containing solution was applied superficially (superfused) to the area of the microinfused tubule. This elevation of peritubular calcium concentration led to an immediate increase of phosphate reabsorption up to 12% of the microinfused phosphate load within 24 min. In another series of experiments, the calcium specific ionophore A23187--a substance which is known to increase intracellular calcium--was superfused on the microinfused tubule. This resulted again in an increase of fractional phosphate reabsorption of about 15% after 24 min. In contrast, when calcium chloride-free as well as ionophore-free solutions were superfused fractional phosphate reabsorption decreased (7%). From these data we conclude that 1. calcium has a direct renal effect on phosphate reabsorption in the absence of parathyroid hormone and 2. intracellular calcium appears to be a major parameter in the regulation of renal phosphate transport under these conditions.

Animals↗
PubMed1979

Renal handling of urate and oxalate: possible implications for urolithiasis.

Both urate and oxalate are organic acids of considerable clinical interest, owing to their limited solubility. Calcium oxalate is the most frequent constituent of renal calculi and occasionally precipitates in body fluids. Urate precipitations are common in the kidney and in various other tissues. In this paper, a short outline of the present knowledge of renal handling of these substances will be followed by some conclusions as to the possible relevance of this knowledge for the understanding of urolithiasis and intrarenal precipitation. Direct (micropuncture) data are available for urate in the rat (1, 6, 7, 10, 21, 23, 28, 36, 42), rabbit (35), dog (34) and cebus monkey (33) and in the rat only for oxalate (11, 15, 20).

Alkalies↗
PubMed1978

Effect of benzolamide on luminal pH in proximal convoluted tubules of the rat kidney.

Luminal pH in early and late proximal tubules was recorded continuously with antimony microelectrodes before and during carbonic anhydrase inhibition. Following i.v. application of benzolamide (25 mumol/kg BW), luminal pH decreased almost immediately in early proximal tubules (deltapH--0.42 +/- 0.06SEM), but increased in late proximal tubules (deltapH +0.27 +/- 0.06). Urinary pH increased (deltapH + 1.6 +/- 0.16) after a delay of some 30 s. Similar results, i.e. decrease of pH in early and increase of pH in late proximal tubules, were obtained, when benzolamide containing solutions were microinfused into early proximal tubules or superfused on the nephron surface. In contrast, luminal pH decreased in late proximal tubules, when benzolamide was microinfused into the same nephron segment. The decrease of luminal pH indicates inhibition of luminally active carbonic anhydrase, leading to delayed buffering of secreted hydrogen ions. The increase of luminal pH in late proximal tubules may be attributed to several factors including increased delivery of bicarbonate, impaired bicarbonate exit at the antiluminal membrane and decreased hydrogen ion formation in the tubular cell due to inhibition of cellular carbonic anhydrase.

Animals↗
PubMed1978

Distal site of calcium reabsorption in the rat nephron.

The site of outflux of 45Ca along the nephron were investigated using microinfusion technique in acutely thyroparathyroidectomized (TPTX), intact and TPTX Wistar rats substituted with parathyroid hormone (PTH). In all three groups 45Ca outflux occurred along the proximal tubule, the loop of Henle and along the distal tubule. After microinfusion into late distal tubules 45Ca recovery in ipsilateral urine was essentially complete for the TPTX group but was only 83 and 65% for the intact and the PTH substituted animals. Increases in microinfusion flow rate from 2--20 nl/min into early and middle distal tubules resulted in increased urinary recovery of 45Ca for all three groups. Similarily, increases in microinfusate Ca concentration from 0.2--2.0 and 5.0 mmol/l resulted in increased fractional urinary recovery of 45Ca both in the presence and absence of PTH. When 45Ca and 3H insulin containing solutions were continuously microinfused into early distal tubules for one hour periods an anticalciuric effect of PTH could be demonstrated. It is concluded that Ca, in addition to its outflux in the proximal tubule and in the loop of Henle, is reabsorbed in the distal tubule accessible to micropuncture. PTH acts anticalciuric at this latter site.

Animals↗
PubMed1978

[Uptake of 2-C14 urate by erythrocytes in hyperuricemia and in gout (author's transl)].

The uptake of 2-C14 urate by erythrocytes was measured in 19 patients with primary hyperuricemia, 6 patients with secondary hyperuricemia, 17 patients with primary gout and 30 controls. The uptake of urate in patients with primary gout was significantly lower than in the controls. In contrast no such difference could be observed in patients with primary and secondary hyperuricemia. The uptake of labeled urate by erythrocytes from gouty patients is especially diminished in the early phase of the uptake kinetics. The possible relevance of this finding for the pathogenesis of urate precipitation in gout is discussed. Further, we consider the application of the tracer urate uptake by erythrocytes as an aid in the early diagnosis of gout.

Erythrocytes↗