Chronic thyroparathyroidectomy and tubular handling of phosphate

The fractional reabsorption (FR) of inorganic phosphate (Pi) along the proximal tubule depends upon both the filtered load of Pi (FLPi) and the tubular reabsorptive capacity of the Pi transporting system. To assess the actual effect of parathyroid hormone on the reabsorptive capacity only, the influence of Pi load has to be eliminated. In this study FRPi was determined by free-flow micropuncture along superficial nephrons of chronically (48 h) thyroparathyroidectomized (TPTX) and pair-fed sham-operated (SHAM) rats at identical FLPi [TPTX 3.07±0.14 (n=26) and SHAM 3.07±0.11 (n=26) mol/min±SEM]. The micropuncture results indicate that in the ranges of tubular fluid over plasma inulin concentration [TF/P)_In] 1.00–1.49 and 1.50–1.99, no difference in FRPi between TPTX and SHAM could be detected. It is only between a TF/P_In of 2.0 and 2.49 that chronic TPTX resulted in a significant increase in FRPi. Accordingly the present study indicates that chronic TPTX increases FRPi in late but not in early portions of proximal tubule. Thus in the early proximal tubule the tubular reabsorptive capacity of the Pi transporting system appears to be unaffected by chronic removal of the parathyroid glands. From this result it can be inferred that the increased plasma concentration of Pi which follows the removal of the parathyroid glands, particularly in the chronic stage, will lead to an apparently paradoxical decrease in FRPi in early proximal tubule as a mere consequence of the increased filtered load of Pi.     

Effects of atrial natriuretic peptide on systemic and renal hemodynamics and renal excretory function in patients with chronic renal failure

Summary We examined the effects of 60 min-hANP infusion (24 ng/min/kg) on glomerular filtration rate (GFR), renal blood flow (RBF), cardiac index (CI) and blood pressure (BP) in 8 patients with chronic renal failure (CRF) with GFR ranging from 18 to 80 ml/min/1.73 m² and in 8 control (C) subjects with normal renal function. Basal plasma levels of ANP and cGMP were elevated in CRF (ANP: 60.6±9.1 vs 13.6±1.9 pmol/l,p<0.05; cGMP: 14.3±2.9 vs 6.6±1.1 pmol/ml,p<0.05). During ANP infusion, peak levels of cGMP were higher in CRF than in C (27.5±3.2 vs. 17.3±1.3 pmol/ml,p<0.05). During ANP infusion, GFR increased in CRF by 70.7±4.2% from 34.5±6.8 to 57.4±9.9 ml/min/1.73m² (p<0.001) as compared to 16.2±1.4% in C (p<0.001 vs CRF). RBF increased in CRF by 43.6±6.4% and in C by 3.1±1.2% (p<0.01). Basal urinary sodium excretion (U_NaV) was slightly lower in CRF than in C but rose to the same level in both groups during ANP infusion. In CRF, as opposed to C, U_NaV remained elevated above baseline after the end of the infusion. The effect of ANP on fractional sodium excretion (FE_Na), however, was more pronounced in C. Basal FE_Na was higher in CRF (12.8±2.5% vs 2.4±1.5% in C,p<0.001), FE_Na remained elevated at 180% over baseline in C sixty minutes after cessation of ANP infusion, while it had returned to baseline in CRF. During ANP infusion, CI increased in CRF after 30 min from 2.91±0.08 to 3.12±0.091/min/m² (p<0.001) and in C from 3.20±0.11 to 3.39±0.13 l/min/m² (p< 0.05). Mean arterial BP was higher in CRF and its decrease was greater than in C (21.1±2.7% vs 9.1±1.0%,p<0.001). In patients with CRF GFR, RPF, and CI remained significantly elevated and BP was still significantly decreased 60 min after ANP infusion. Total peripheral vascular resistance (TPR) was elevated in CRF and declined during ANP infusion in both CRF and C. The decline of TPR was sustained and more pronounced in CRF than in C. Renal vascular resistance (RVR) was high in CRF and dropped by nearly 50% during ANP infusion, whereas only a moderate decline in RVR during ANP application was observed in C. Thus, exogenous ANP had greater and prolonged effects on systemic hemodynamics and renal function in CRF than in C. They may be due to higher levels of ANP following ANP infusion and appear to be mediated by a more sustained formation of the second messenger cGMP.Abbreviations ANP atrial natriuretic peptide - CRF chronic renal failure; - GFR glomerular filtration rate - FF filtration fraction - ERPF effective renal plasma flow - ERBF effective renal blood flow - BP blood pressure - MAP mean arterial blood pressure - HR heart rate - SV stroke volume - CO cardiac output - CI cardiac index - TPR total peripheral resistance - RVR renal vascular resistance - U_NaV urinary sodium excretion - FE_Na fractional sodium excretion - PRA plasma renin activity - ECFV extracellular fluid volume - PAH paminohippuric acid Dedicated to Prof. Dr. med. F. Krück on the occasion of his 70th birthday     

Proximal tubular transport and urinary excretion of sodium after renal denervation in sodium depleted rats

The effect of unilateral renal denervation on renal handling of water, sodium and potassium was studied with clearance and micropuncture techniques in sodium depleted anaesthetized rats in the nondiuretic state. In clearance experiments renal denervation resulted in a +140 and +320% increase in urine flow and potassium excretion, but sodium excretion of innervated (I) and denervated (D) kidneys was similar (I: 12.0±2.0, D: 14.0±3.6 nM·min^–1·g^–1; NS). However, upon the loop diuretic furosemide (1 mg·kg^–1), a marked denervation natriuresis was observed (I: 2.8±0.9, D: 5.9±1.0 M·min^–1;P<0.05) and denervation diuresis and kaliuresis persisted, too (+95 and +60%, respectively). Micropuncture results revealed that fractional reabsorption of filtrate to late proximal puncture site was depressed by renal denervation from 62 to 49% while no change in time control rats was seen (64±2 vs. 64±1%; NS). In micropuncture experiments besides augmented urine flow (+82%) from D kidneys also a small denervation natriuresis was present (I: 21.6±6.4, D: 29.2±7.0 nM·min^–1;P<0.05). It is concluded that the lack or marked attenuation of denervation natriuresis in sodium depleted rats were the result of an almost complete compensatory distal reabsorption of the excess sodium (but not of water and potassium) leaving the proximal tubule after denervation. The distal adaptive response can be overcome by furosemide.     

Dissociation between antidiuretic response and renal medullary cyclic AMP levels in the rat

Renal tubular bicarbonate reabsorption and acidification were evaluated in phosphate depleted rats (PD) and controls. After 33 days of phosphate depletion, urine pH of PD rats (N=5, 6.36±0.15) was significantly higher than control (N=5, 5.64±0.09,P<0.005) following an NH₄Cl load. Urinary titratable acid of PD rats (9.6±1.8) was significantly reduced compared to control (117.2±19.7 Eq/3 h,P<0.001), whereas NH ₄ ⁺ excretion was not different. The plasma HCO ₃ ^– thresholds at which bicarbonaturia occurred (approximately 25 mEq/l) were identical in controls and phosphate depleted rats during isotonic bicarbonate infusion. The higher urine pH of phosphate depleted rats following NH₄Cl administration was not due to low urinary phosphate as 3-day phosphate depleted rats could normally acidify urine after NH₄Cl (pH=5.86±0.09,N=6 vs. control 5.87±0.08,N=6,P=N.S.) despite urinary phosphate excretion as low as in 33-day PD rats. These data indicate the presence of impaired distal tubular acidification in chronically phosphate depleted rats.Former trainee of the Cardiovascular Research Program and currently a third year medical student at The University of Michigan Medical School.     

Renal intracortical blood flow distribution,function and sodium excretion in response to saline loading of anesthetized and unanesthetized dogs

Summary In order to study the effect of anesthesia on the canine response to saline loading, experiments were performed on 10 dogs, first while awake and then during pentobarbital anesthesia. Individual kidney function and intrarenal blood flow response to saline loading (7.5% body weight) were measured in each condition and all data are reported as the average of a single kidney. C_IN is considerably reduced under anesthesia (24.7±3.2 vs. 43.2±3.9 ml/min,P<0.01). A directionally similar reduction of PAH clearance was noted (89±17 vs. 122±13 ml/min). The natriuretic response to saline loading of the dogs reached 290±61 Eq/min while awake, but only 70±27 Eq/min while anesthetized. No measurable increase of C_IN or C_PAH occurred in response to saline loading either in the anesthetized or unanesthetized state. The natriuresis was entirely due to a rise of C_NA/GFR in both circumstances. The change of C_NA/GFR in response to saline load was also appreciably larger while awake (1.24.7% vs. 0.71.8%). Although the fraction of blood flow to the outermost quarter of the kidney was initially the same (31±3 vs. 29±3%) awake or anesthetized, the changes with saline loading were in the opposite direction and the values reached were significantly different (37±3, awake, vs. 27±3%,P<0.05). We conclude that while increased outer cortical blood flow is not necessary for natriuresis, it may occur during sodium loading and may facilitate sodium excretion.Supported by VA Program 3385-01     

Stimulation of tubular reabsorption of magnesium and calcium by antidiuretic hormone in conscious rats

The effect of antidiuretic hormone on urinary electrolyte excretion was investigated by clearance techniques in conscious rats in metabolic cages. Brattleboro rats with hereditary diabetes insipidus (DI) (no ADH) were studied in the absence of exogenous ADH (control group = C,n=4), and after several weeks of continuous dDAVP infusion (period A) followed by discontinuation of dDAVP (period B) (experimental group = E,n=6). dDAVP, a non-pressor antidiuretic analogue to ADH, induced 1) a high urine concentration (2,645±44 (SEM) in group E vs 131±6 mosmol/kg H₂O in group C),P<0.001; 2) no significant change in plasma osmolality (288±2 vs 297±7 mosmol/kg H₂O respectively) and in plasma concentration of major electrolytes, Na, K, Cl, Mg, and Ca; 3) a large decrease in urinary excretion of calcium and magnesium and no change in other electrolyte or total osmolar excretion. Fractional excretions in rats of groups C and E during period A were, respectively, for Na: 0.59±0.03 (SEM) and 0.51±0.33% (NS), for Ca: 2.92±0.62 and 0.34±0.05% (P<0.001) and for Mg: 7.75±0.83 and 1.38±0.28% (P<0.001). After treatment discontinuation, plasma osmolality in group E rose to 304±2 mosmol/kg H₂O (P<0.01 compared to period A) with slight increases in plasma Na and Cl concentrations. Urine osmolality fell below, and urine flow rate rose above values observed in the control group. Fractional excretion of Ca and Mg rose to values seen in DI rats (3.30±0.37%, NS, for Ca) or above (26.95±0.65%,P<0.001, for Mg), with no change in other solute fractional excretion. Other works, from our and other's groups have shown that 1) long-term exposure to dDAVP induces a marked hypertrophy of the epithelium of the thick ascending limb of Henle's loop in its medullary part (MTAL) and 2) dDAVP induces an increase in Ca and Mg tubular reabsorption between end proximal and early distal sites of micropuncture. Taken together, these results suggest that the effects of ADH on divalent cation fractional excretion, seen in the present study, probably results from an increased Ca and Mg voltage-dependent reabsorption in the MTAL. This reabsorption is linked to the increased salt transport induced in this segment, both by a direct effect of ADH and by an indirect effect resulting from the increased solute delivery to the MTAL in the concentrating kidney.     

Effect of dietary sodium content on renal handling of lithium

Previous studies have shown that the clearance of lithium (C_Li) is a quantitative measure of the delivery of tubular fluid to Henle's loop in rats given food with an ordinary or high sodium content but not in rats given food with a low sodium content, because under these circumstances lithium is also reabsorbed to some extent in the distal nephron segment. The present study examines C_Li, C_Na and urine flow in diabetes insipidus rats at various dietary sodium contents. The results showed that C_Li was 120 l/min/100 g b.w. when no distal reabsorption took place at a dietary sodium content of 300 mmol/kg. At a dietary sodium content of 5 mmol/kg the calculated distal lithium reabsorption reduced C_Li by 55 l/min/100 g b.w.; at 25 mmol/kg distal reabsorption was reduced to half this value; at 50 mmol/kg distal reabsorption was slight and barely significant, and at 75–300 mmol/kg there was no distal reabsorption of lithium. It is concluded that C_Li can be used as a quantitative measure of the delivery of tubular fluid to the loop of Henle at dietary sodium contents higher than 50–75 mmol/kg in the rat.     

Parathormone as a mediator of inorganic phosphate diuresis during saline infusion in the rat

Summary Normal rats were infused with isotonic saline at 0.50 ml/min for 2 hours in order to expand their extracellular fluid volume. Under these conditions fractional excretion of inorganic phosphate was found to be as high as 38.8±3.0% of filtered phosphate, while fractional sodium excretion was 12.9±0.7% of filtered sodium. The combined addition of calcium and magnesium to the infusion solution decreased inorganic phosphate excretion significantly (P<0.001) to 11.2±3.6% (presumably by inhibiting parathyroid gland activity), while sodium excretion was unchanged (13.5±1.1%). Parathyroidectomized rats were infused with isotonic saline at 0.50 ml/min to achieve a similar extent of extracellular fluid volume expansion as in the normal rats. In these animals inorganic phosphate excretion was as low as 0.9±0.9% of filtered phosphate, while sodium excretion was 11.8±2.2% of filtered sodium. Administration of parathormone to volume expanded parathyroidectomized rats resulted in marked increases or inorganic phosphate excretion to 41.5±3.1% of filtered phosphate (P<0.001), while sodium excretion remained unaltered (12.0±2.8% of filtered sodium), thus resembling very closely the results in normal volume expanded rats.From these results it is concluded, that saline induced phosphaturia in normal rats is mediated primarily by parathormone. Furthermore, sodium excretion during volume expansion of extracellular fluid appears to be independent of inorganic phosphate excretion and independent of changes in parathyroid activity.This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft.     

A comparison of micropuncture and lithium clearance methods in the assessment of renal tubular function in rats with diabetes insipidus

The lithium clearance technique has been proposed as a non-invasive method whereby fluid delivery from the pars recta and pars convoluta of proximal tubules can be measured as C_Li and C_IN [0.78 C_Li/C_IN+0.22], respectively [12], C_Li being the clearance of lithium and C_IN that of inulin. In the present study, fluid delivery from proximal tubules was estimated simultaneously by micropuncture and lithium clearance techniques in anaesthetized Brattleboro rats with diabetes insipidus, under control conditions and following chronic treatment with hydrochlorothiazide. Absolute deliveries from the proximal convoluted tubules as determined by the micropuncture and lithium clearance methods were 437 and 427 μl/min, respectively, in untreated animals and 348 and 355 μl/min, respectively, in thiazide-treated animals. The individual results obtained by the two methods showed a high degree of correlation (r=0.85,P<0.001). In untreated Brattleboro rats, proximal fluid delivery as estimated by both the micropuncture and lithium clearance techniques showed significant (P<0.001) correlations with urine flow rate. These results provide further evidence for the acceptance of lithium clearance as a valid estimate of proximal tubular fluid delivery.     

A pharmacological study of the control of nasal cooling in the dog

Summary Clearance studies were performed in order to examine the effect of expansion of extracellular fluid volume (ECFV) on the maximal reabsorptive capacity for inorganic phosphate (Tm_Pi) in acutely parathyroidectomized (PTX) and intact rats. Tm_Pi values were obtained in both control and volume expansion. In PTX rats, the Tm_Pi values in control and expansion were 8.25±1.52 and 6.14±1.02 mol/min (mean values ±S.D.), respectively; the Tm_Pi/ GFR values were 2.96±0.31 and 2.09±0.30 mol/ml, respectively. Inintact rats, the Tm_Pi values in control and expansion were 3.56±0.94 and 2.98 ±0.94 mol/min, respectively, and the Tm_Pi/GFR values were 1.34±0.23 and 1.05±0.23 mol/ml, respectively. From these results it is concluded that expansion of ECFV decreases the Tm_Pi values both in the absence and presence of parathyroid hormone.This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft (Fr 239/5)     

[51Cr]EDTA for measuring total and single nephron glomerular filtration rate in the rat

Clearance and micropuncture experiments were performed in halothane anaesthetized rats. The aim was a comparison of paired estimates of glomerular filtration rate (GFR) from the renal clearance of [⁵¹Cr]EDTA (C_[51Cr]EDTA) with simultaneous estimates of polyfructosan ((Inutest) C_In), ³H,- and ¹⁴C-labelled inulin clearance (C_[3H]In and C_[14C]In, respectively) and proximal tubular fluid/plasma concentration ratios (TF/P) of [¹⁵Cr]EDTA and TF/P ratios of ¹⁴C-labelled inulin measured in the same samples. C_[51Cr]EDTA correlated well with, but underestimated C_In by ? 10%. The correlation coefficient (r) was 0.92. C_[51.Cr]EDTA also correlated with, and underestimated C_[14C]In by 6%, r= 0.88, whereas it overestimated C_[3H]In by 5%, still with a close correlation (r= 0.92). Paired data on proximal (TF/P) ratios of [¹⁵Cr]EDTA and [¹⁴C]inulin were collected from early, mid and late proximal convolutions. The data were scattered around the line of identity, r= 0.91. It is concluded that [¹⁵Cr]EDTA is a valid alternative for estimates of total renal and single nephron GFR in rats and has the advantage of being less expensive than [¹⁴C]inulin.     

Micropuncture studies on the filtration rate of single superficial and juxtamedullary glomeruli in the rat kidney

Summary Single nephron filtration rates of superficial and juxtamedullary nephrons were determined in high and low sodium rats. Single nephron GFR was calculated from TF/P inulin and tubular flow rate in superficial nephrons and single juxtamedullary GFR from corresponding data in long loops of Henle. In low sodium rats superficial nephron GFR was 23.5±6.4 (SD)×10^–6 ml/min×g KW, juxtamedullary nephron GFR was 58.2±13.6 and total kidney GFR (C _In) was 0.94±0.16 ml/min×g KW. Using these single nephron values, total kidney GFR and a total number of 30,000 glomeruli per kidney, the number of superficial and juxtamedullary glomeruli was calculated to be 23,267 and 6,733, respectively. During high sodium diet superficial nephron GFR increased to 38.1±11.3 and single juxtamedullary GFR decreased to 16.5±6.6, total kidney GFR increasing to 1.01±0.24. Calculation again revealed the same distribution of the two nephron types. End-proximal TF/P inulin in superficial nephrons was 2.36±0.36 in low sodium and 2.31±0.28 in high sodium rats. Loops of Henle TF/P inulin and intratubular flow rate were inversely related: the highest TF/P inulin values and lowest intratubular flow rates were found in the descending limb. These data quantify the distribution of superficial and juxtamedullary nephrons on a functional basis and suggest a mechanism by which the kidney adjusts sodium excretion by altering the contribution of each nephron type to total kidney GFR.Supported by the Deutsche Forschungsgemeinschaft and the U.S. Department of the Army, through its European Research Office.     

Examination of possible renal origin of the humoral factor responsible for saline diuresis in the dog

Summary The hypothesis of renal origin of the humoral factor responsible for the natriuresis which follows saline infusion in the dog was tested in a cross-circulation model especially designed for the purpose. Renal venous blood of saline loaded donor dogs was pumped directly into the system perfusing the right (assay) kidney of oliguric recipient animals. In control and recovery periods, recipients own renal venous blood was substituted for the blood of saline-infused donors.Sodium excretion increased slightly from the control value of 2.8±1.2 (S.D.) to 4.7±3.5 Eq/min (68 per cent increase,p<0.05), but only slight recovery toward control rate was noted within 25 min of cessation of cross-circulation. Simultaneously, filtered sodium decreased slightly from 2.8±1.15 (S.D.) to 2.7±1.10 mEq/min. Glomerular filtration rate (C _CR) and effective renal plasma flow (C _PAH) decreased gradually during the experiment. Urine flow,U/P _osm, hematocrit, and perfusion pressure of the assay kidney showed only minor changes.Since the slight increase in sodium excretion during cross-circulation constituted but a small fraction of natriuresis observed in saline-loaded donors, it was concluded that the results are incompatible with the release from the kidney of saline-infused animals of a potent natriuretic factor.This study was supported by American Heart Association Grant 66630.     

Sodium chloride as regulator of renal prostaglandin E2 production in patients with essential hypertension

Summary The effect of dietary sodium intake (5 days' low salt, 4 days' high salt) on 24-h urinary prostaglandin E₂ (PGE₂) and prostaglandin F₂ (PGF₂) excretion, blood pressure (BP), and plasma renin activity (PRA) was evaluated in 16 patients with essential hypertension. Sodium restriction significantly increased urinary PGE₂ excretion (p<0.05) from 151±76 to 328±94 ng/24 h, while high salt intake reduced renal PGE₂ production to 114±41 ng/24 h (p<0.05). There was a moderate but not significant increase in urinary PGF₂ excretion on the low salt regimen, which was reversed under high salt diet. Systolic and diastolic blood pressure fell from 162±11 to 145±10 mm Hg, i.e., 102±6 to 90±9 mm Hg on low sodium intake (35 mEq/day) and returned to levels close to control after 4 days on a high salt diet (250 mEq/day). Under low salt conditions, PRA increased significantly (p<0.001) from 0.83±0.33 to 2.82±1.12 ng AI/ml/h and fell to 0.45±0.31 ng AI/ml/h on high salt regimen (p<0.001).The results demonstrate that dietary sodium chloride intake modulates renal PGE₂ production in patients with essential hypertension. The depressed PGE₂ production under high salt conditions may play a role in regulation of renal vascular resistance and influence sustainment of chronic hypertensive disease.Supported by Deutsche Forschungsgemeinschaft     

β2-microglobulin and other proteins in serum and urine during preeclampsia

Summary Serum and urine samples of 5 patients with preeclampsia, an equal number with preeclampsia superimposed upon chronic pyelonephritis, and 20 normal pregnant women were analysed for fibrin split products (immunoelectrophoresis) and other proteins (Oudin-method) including ₂-microglobulin (radioimmunoassay).No fibrin split products could be detected in normal pregnant women or those with preeclampsia superimposed upon chronic pyelonephritis. Distinctly abnormal values were found, however, in the patients with preeclampsia (split D, 27.2±5.1 mg% (S.D.) in serum and 162±55mg/24 h (S.D.) in urine; split E, 0.3±0.1 mg% (S.D.) in serum and 4.2±3.1 mg%/24 h (S.D.) in the urine; fibrinogen in serum 532±146 mg% and in urine 340±78 mg/24 h (S.D.).Mean total protein excretion of patients with preeclampsia (1951±322 mg S.D./24 h) was not different from the value of patients with preeclampsia superimposed upon chronic pyelonephritis (1781±289 mg S.D./24 h).Urinary ₂-microglobulin excretion of patients with simple preeclampsia (glomerular filtration rate 100 ml/min) was 4 to 5-fold increased at term but more than 100-fold in patients whose preeclampsia was superimposed upon chronic pyelonephritis (glomerular filtration rate 30–70 ml/min).The transient urinary excretion of fibrin split products and other proteins in patients with preeclampsia and normal glomerular filtration rate is an indication of a reversible glomerular lesion, whereas the increased ₂-microglobulin excretion in this group of patients is due to a tubular lesion. In patients with preeclampsia superimposed upon chronic pyelonephritis the excretion of ₂-microglobulin is further increased which may be explained by an additional lesion of the already impaired tubular function during delivery.In serum, prealbumin was decreased to about 55% and albumin to 60% in the patients with preeclampsia and preeclampsia superimposed upon chronic pyelonephritis which cannot be explained by renal loss alone but is very likely due to an inhibition of protein synthesis in the liver cell.Contains parts of the Doctoral Thesis of D. Prüfer     

Nierenfunktion bei unterschiedlicher Hydratation unter Berücksichtigung volumenregulatorischer Gesichtspunkte

Zusammenfassung 1. Bei 35 gesunden Personen im Alter von 15–51 Jahren werden in insgesamt 45 Simultanbestimmungen die gegenseitigen Beziehungen zwischen der Größe des physiologisch aktiven Anteils des Extracellulärraumes (ECR), PAH- und Inulinclearance (C_{PAH, In}) und Urinvolumen (U) unter verschiedenen Hydratationszuständen untersucht. Durch perorale Zufuhr unterschiedelicher Wassermengen am Vorversuchstag und vor Versuchsbeginn schwankt der Harnfluß zwischen 0,667 und 10 ml/min.2. Die unter diesen Bedingungen gemessenen Mittelwerte betragen für den ECR 15,53±1,56% des Körpergewichtes, für C_In 122,1±16,5 ml/min/1,73 m² und für C_PAH 667,1±108,5 ml/min/1,73 m² und liegen damit im physiologischen Normalbereich.3. In Abhängigkeit vom Hydratationsgrad bestehen innerhalb der sog. physiologischen Schwankungsbreite der Clearancewerte statistisch signifikante positive Korrelationen zwischen ECR und C_In (P<0,01), ECR und U (P<0,0027) sowie zwischen C_In und U (P<0,01).4. Obwohl bei verschiedener Hydratation eine hochsignifikante positive Korrelation zwischen C_PAH und C_In (P<0,001) nachweisbar ist, kann zwischen ECR und C_PAH und zwischen C_PAH und U keine statistische Beziehung festgestellt werden. Mathematisch lassen sich hierbei 37,9% der Veränderungen von C_In aus gleichzeitigen Veränderungen von C_PAH erklären.5. Mit steigendem Urinvolumen besteht bei gleichbleibendem Widerstand in den Nierenvenolen eine Tendenz zur Abnahme des afferenten Gefäßwiderstandes zugunsten einer Widerstandserhöhung im Vas efferens.6. Die Beeinflussung der Glomerulusfiltratmenge durch die Größe des extracellulären Flüssigkeitsvolumens wird im Sinne eines neurogenen Reglermechanismus, der hauptsächlich im Dienste der Aufrechterhaltung einer Homoiostase des Natriumhaushaltes stehen dürfte, diskutiert.     

Maleic acid induced aminoaciduria,studied by free flow micropuncture and continuous microperfusion

The injection of 200 mg/kg BW maleic acid was found to be a suitable dose for exploring the experimental Fanconi syndrome by micropuncture techniques in rats. In clearance experiments, the fractional excretion of glycine,l-alanine,l-aspartate and taurine was measured. After intraperitoneal administration of maleic acid the excretion of these amino acids was increased in the range between the 20-fold and the 230-fold. Free flow micropuncture experiments showed that the reabsorption of these amino acids is reduced drastically along the whole proximal tubule. Continuous microperfusion experiments lead to the result that, in maleic acid pretreated rats, the reabsorption of¹⁴C-glycine from the proximal convolution was strongly inhibited. It was found, furthermore, that after blocking the saturable glycine transport byl-phenylalanine, the remaining reabsorption of glycine (corresponding to passive diffusion) was exactly the same with and without maleic acid. Microinfusion experiments with 8 mol·l^–1 l-³H-alanine into the early distal tubule showed a fractional recovery of 103±4.2% (S.D.) in the control and of 101±6.5% in presence of maleic acid. It is concluded that maleic acid inhibits the saturable reabsorption mechanism of amino acids along the proximal tubule. Passive permeability of the tubular membrane does not seem to be altered by maleic acid.Part of this work was presented at the 49th Meeting of the German Physiological Society in Göttingen, March, 7–10, 1978 [22]     

Atrial natriuretic peptide in human urine

Summary A highly sensitive radioimmunoassay to measure atrial natriuretic peptide (ANP) concentration in urine has been established, and its clinical usefulness is presented. ANP in urine was stable at 4° C for several days and was easily measured by our radioimmunoassay. The average ANP excretion in 65 healthy persons was 25.0±1.4 ng/day (mean ± SEM) and the fractional excretion of ANP was 0.7±0.05%. In 14 patients with congestive heart failure, the average ANP excretion was 119.2±29.4 ng/day, which decreased to 53.3±11.0 after successful treatment.Abbreviations ANP atrial natriuretic peptide - hANP human atrial natriuretic peptide - RIA radioimmunoasay - NSB non specific bound - FE_ANP the fractional excretion of atrial natriuretic peptide - FE_Na the fractional excretion of sodium - SIADH the syngrome of inappropriate secretion of antidiuretic hormone     

The anthropometrical and physiological characteristics of elite water polo players

In order to examine the physical and physiological demands of water polo, we assessed the profile of elite water polo players. Nineteen male professional water polo players (age: 25.5±5.0 years, height: 184.5±4.3 cm body mass: 90.7±6.4 kg) underwent body composition assessment by dual-energy X-ray absorptiometry. We also evaluated peak oxygen consumption O_2peak, lactate threshold (LT), energy cost of swimming (C_s), anaerobic capacity and isokinetic shoulder strength. Body fat (%) was 16.8±4.4, lean mass (LM) 75.1±4.9 kg and bone mineral density (BMD) 1.37±0.07 g·cm^–2 . O_2peak was 57.9±7 ml·kg^–1· min^–1 . LT was identified at 3.9±0.7 mmol·l^–1 at a swimming velocity (v) of 1.33±0.05 m·s^–1 with a heart rate of 154±7 bpm, corresponding to an intensity of 83±9 of O_2peak. The average C_s of swimming at the LT was 1.08±0.04 kJ·m^–1 . C_s at LT was correlated to body mass index (BMI) (r=0.22, P=0.04) and to swimming performance at 400 m (r=0.86, P=0.01) and 4×50 m (r=0.84, P<0.01). Internal rotator muscles were stronger compared to the external rotators by a 2:1 ratio. This study provides a quantitative representation of both physical and physiological demands of water polo and proposes a comprehensive battery of tests that can be used for assessing the status of a team.     

The influence of long-term infusion of the calcium antagonist diltiazem on postischemic acute renal failure in conscious dogs

Summary The influence of long-term infusion of the calcium-entry blocker diltiazem on postischemic acute renal failure was investigated in conscious dogs monitored by implanted instruments. In 18 uninephrectomized beagle dogs on a salt-rich diet, an electromagnetic flow probe and an inflatable plastic cuff were placed around the renal artery. Acute renal failure was induced by inflating the cuff for 180 min in the conscious animal. Group A (n=5, control) received an intraaortic injection of 0.9% NaCl (5 ml/day) from the 3rd day before until the 7th day after ischemia and group B (n=6, posttreatment) an intra-aortic injection of diltizem (5 µg·min^–1·kg^–1) beginning at the end of ischemia until the 7th day. Group C (n=7, pre- and posttreatment) received diltiazem from the 3rd day before until the 7th day after ischemia. In group A, renal blood flow dropped from 149±16 (preischemic) to 129±29 ml·min^–1 on the 1st day after ischemia. In contrast, renal blood flow increased on the 1st postischemic day in both treatment groups by 29±15% (group B,P 0.05) and 14±13% (group C). In the following days, there was no significant difference in renal blood flow between groups A, B and C. In group B, the reduction of the glomerular filtration rate was similar to that in the control group. In group C, the glomerular filtration rate was significantly less reduced than in group A (34±1.8 preischemically to 17±5.4 on day 1,P 0.05 and 20±4.1 ml·min^–1 on day 7,P 0.05). Plasma renin activity increased in both diltiazem groups, more pronounced so in group B (from 3.7±1.0 on day 1 to 16.2±7.9 ng ATI·ml^–1·h^–1 on day 7,P 0.05). In contrast to groups A and B, the increase in fractional sodium excretion was less pronounced in group C. Likewise, the decrease in free water-reabsorption was less marked than in groups A or B. It was apparent that diltiazem, when administered pre- and post-ischemically, preserved glomerular filtration rate and renal blood flow. When diltizem was given solely postischemically there was an improvement in renal blood flow, but no significant influence on glomerular filtration rate. We therefore conclude that mainly tubular factors, in addition to the attenuation of postischemic vasoconstriction, are involved in the protective effect of diltiazem on postischemic acute renal failure in conscious dogs.Abbreviations ARF acute renal failure - C_osmol clearance of osmolarity - E_Na urinary excretion rate of sodium - FE_Na fractional excretion rate of sodium - GFR glomerular filtration rate - HR heart rate - NE norepinephrine - PAM mean arterial blood pressure - PRA plasma renin activity - RBF renal blood flow - RVR renal vascular resistance - T_H2_O free water reabsorption - V_U urine volume