Proximal Reabsorption Research Articles

The effect of shear stress on the basolateral membrane potential of proximal convoluted tubule of the rat kidney

As consequence of glomerular filtration the viscosity of blood flowing through the efferent arteriole increases. Recently, we found that shear stress modulates proximal bicarbonate reabsorption and nitric oxide (NO.) was the chemical mediator of this effect. In the present work, we found that agonists of NO. production affected basolateral membrane potential (V (blm)) of the proximal convoluted tubule (PCT) epithelium. Using paired micropuncture experiments, we perfused peritubular capillaries with solutions with different viscosity while registering the V (blm). Our results showed that a 50% increment in the viscosity, or the addition of bradykinin (10(-5) M) to the peritubular perfusion solution, induced a significant and similar hyperpolarization of the V (blm) at the PCT epithelium of 6 +/- 0.7 mV (p < 0.05). Both hyperpolarizations were reverted by L-NAME (10(-4) M). Addition of 2,2'-(hydroxynitrosohydrazino) bis-ethanamine (NOC-18) 3 x 10(-4) M to the peritubular perfusion solution induced a hyperpolarization of the same magnitude of that high viscosity or bradykinin. These results strongly suggest the involvement of NO. in the effect of high viscosity solutions. This effect seems to be mediated by activation of K+(ATP) channels as glybenclamide (5 x 10(-5) M) added to peritubular solutions induced a larger depolarization of the V (blm) with high viscosity solutions. Acetazolamide (5 x 10(-5) M) added to high viscosity solutions induced a larger hyperpolarization (8 +/- 1 mV; p < 0.05), suggesting that depolarizing current due to HCO(-)3 exit across the basolateral membrane damps the hyperpolarizing effect of high viscosity. Considering that Na(+) and consequently water reabsorption is highly dependent on electrical gradient, the present data suggest that the endothelium of kidney vascular bed interacts in paracrine fashion with the epithelia, affecting V (blm) and thus modulating PCT reabsorption.

Combined Effects of Carbonic Anhydrase Inhibitor and Adenosine A1 Receptor Antagonist on Hemodynamic and Tubular Function in the Kidney

Background: Carbonic anhydrase inhibitors (CAI) reduce proximal reabsorption, activating tubuloglomerular feedback (TGF) and reducing glomerular filtration rate (GFR). Adenosine A₁ receptors (A₁R) mediate the TGF response and stimulate proximal reabsorption. Methods: Clearance and micropuncture studies were performed in Wistar rats to determine whether blockade of A₁R (KW3902 0.3 mg/kg i.v.) would prevent CAI (benzolamide 5 mg/kg i.v.) from lowering GFR, whether CAI and KW3902 exert additive effects on sodium excretion, and to what extent such interactions depend on events in the glomerulus, proximal tubule, or distal nephron. Results: KW3902 raised GFR and prevented CAI from lowering GFR. KW3902 and CAI caused additive diuresis and natriuresis. KW3902 and CAI increased lithium clearance, but their effects were redundant. CAI increased the dependence of proximal reabsorption on active chloride transport. KW3902, alone, did likewise, but to a lesser extent than CAI. Adding KW3902 to CAI lessened the shift toward active chloride transport. Conclusions: The data reveal that A₁R mediate glomerular vascular resistance whether or not TGF is activated, that additive effects of CAI and KW3902 on salt excretion occur, in part, because KW3902 inhibits reabsorption downstream from the macula densa, and that KW3902 likely inhibits proximal reabsorption by interfering with apical sodium-hydrogen exchange.

Elevated Serum Adiponectin Level is Associated with a Decrease in Rate of Proximal Tubular Sodium Reabsorption

Elevated Serum Adiponectin Level is Associated with a Decrease in Rate of Proximal Tubular Sodium Reabsorption

An unexpected role for angiotensin II in the link between dietary salt and proximal reabsorption

We set out to confirm the long-held, but untested, assumption that dietary salt affects proximal reabsorption through reciprocal effects on the renin-angiotensin system in a way that facilitates salt homeostasis. Wistar rats were fed standard or high-salt diets for 7 days and then subjected to renal micropuncture for determination of single-nephron GFR (SNGFR) and proximal reabsorption. The tubuloglomerular feedback (TGF) system was used as a tool to manipulate SNGFR in order to distinguish primary changes in net proximal reabsorption (Jprox) from changes due to glomerulotubular balance. The influence of Ang II over Jprox was determined by the sensitivity of Jprox to the AT1 receptor antagonist, losartan. Plasma, whole kidneys, and fluid from midproximal tubules were assayed for Ang II content by radioimmunoassay. In rats on the standard diet, losartan reduced Jprox by 25% and reduced the maximum range of the TGF response by 50%. The high-salt diet suppressed plasma and whole-kidney Ang II levels. But the high-salt diet failed to reduce the impact of losartan on Jprox or the TGF response and actually caused tubular fluid Ang II content to increase. The persistent effect of Ang II on Jprox prevented a major rise in late proximal flow rate in response to the high-salt diet. These observations challenge the traditional model and indicate that the role of proximal tubular Ang II in salt-replete rats is to stabilize nephron function rather than to contribute to salt homeostasis.

Biochemical, functional, and histochemical effects of essential fatty acid deficiency in rat kidney

The present study was designed to examine the effects of EFA deficiency (EFAD) on biochemical, functional, and structural aspects of the kidney in growing and adult rats fed a normal or EFAD diet for 9 wk after weaning. Food and fluid intake (F1), urine volume, and Na+ and K+ excretions were measured weekly from weeks 4 to 8 by placing the rats in individual metabolic cages for 24 h. At week 9, Li+ and a 5% water load, respectively, were administered at 14 and 1.5 h prior to glomerular and proximal tubular function studies, as assessed by 3-h creatinine (C(Cr)) and Li+ (C(Li+)) clearances. Hematocrit and urine volume; serum and urine [Cr], [Li+], [Na+], and [K+]; and renal FA distribution were also measured. Data [corrected to 100 g/body weight (bw) and presented as means +/- SEM] were significant, at P< or = 0.05. Despite a similar ingestion of solids from weeks 4 to 7 (weeks 7 to 10 of life), the rats on the EFAD diet showed a decreased body weight from week 5. From weeks 4 to 8, Fl and urine volume were similar for both groups, but the Fl increased at week 6 in the EFAD group; 24-h Na+ and K+ excretions were similar at all weeks, except for an increase in the EFAD group for both ions at week 7. In the EFAD group, CCr and CLi+ decreased by 27 and 56.3%, respectively (385.7 +/- 33.4 vs. 280 +/- 21.1, and 21.0 +/- 2.1 vs. 9.2 +/- 1.1 microL/min/100 g; n = 9 vs. 10), the latter result suggesting increased proximal reabsorption. The 3-h Na+ and K+ excretions were similar, but the Li+ decreased (0.78 +/- 0.06 x 10(-2) vs. 0.32 +/- 0.03 x 10(-2) microeq/min/100 g) in the EFAD group, giving additional support to the suggestion. Renal structure was normal and similar for both groups, but the EFAD group showed a more prominent proximal tubule brush border, together with heavier periodic acid-Schiff staining in all specimens from weeks 5 to 9. In the EFAD group, FA of the n-9 and n-7 series were higher, but most of the n-6 series were lower as a percentage of total lipids in the medulla and cortex. Medullary levels of 20:4n-6 were maintained, 22:4n-6 declined twice, arachidonic acid was maintained, and 20:5n-3 was lower. The EFAD diet affected glomerular function, proximal tubular structure and function, and FA distribution in the rat kidney.

Impaired Glomerular and Tubular Function as a Short-Term Effect of Sirolimus Treatment in the Rat

Aims: To investigate acute and short-term effects of sirolimus (SRL) on glomerulo-tubular function, blood pressure (BP), and renal morphology in the rat. Methods: Male Sprague-Dawley rats, weighing initially 140–180 g were treated with SRL in three series: SRL 0.2, 0.4, or 0.8 mg/kg/day intraperitoneally for up to 28 days after skin allo-transplantation from Lewis donors (to establish a dosage with significant immunosuppressive effect). SRL 0.4 mg/kg intravenously (acute effects). SRL 0.4 mg/kg/day intraperitoneally for 7 days (short-term effects). Inulin, lithium (C_Li) and sodium clearance, and intra-arterial BP were measured in conscious catheterized rats. Morphological kidney studies were completed after post-mortem fixation. Results: Maximum immunosuppressive effect was achieved with SRL 0.4 mg/kg/day. SRL acutely increased GFR and C_Li, whereas fractional proximal reabsorption (PFR) declined. In the short-term study SRL had opposite effects on GFR and C_Li, unaffected proximal tubular reabsorption and PFR, raised BP, diminished food consumption, and slower increase in body weight. Morphological changes were non-specific. Conclusion: In a dosage giving maximum immunosuppressive effect, SRL revealed acute effects on glomerular and proximal tubular function thus indicating increased outflow from the proximal tubules whereas one week of SRL treatment produced a change resembling the known nephrotoxic effects of the calcineurine inhibitors.

Recent Advances in Renal Phosphate Transport

Phosphate (Pi) homeostasis is achieved by adjusting the intestinal absorption and the renal excretion. Renal proximal reabsorption of Pi is regulated by controlling the amount of NaPi-IIa cotransporters in the brush border membrane of proximal tubules. Therefore, the understanding of the molecular mechanisms that control the apical expression of NaPi-IIa is required to have a full picture of how phosphate balancing takes place. In this review we will summarize our present knowledge about the mechanisms involved in the regulation of the apical expression and membrane retrieval of this family of transporters.

Endogenous beta-2 adrenergic receptor involved in abnormal proximal tubule sodium reabsorption in SHR

Endogenous beta-2 adrenergic receptor involved in abnormal proximal tubule sodium reabsorption in SHR

Glomerular hyperfiltration in type 1 diabetes mellitus results from primary changes in proximal tubular sodium handling without changes in volume expansion

Glomerular hyperfiltration plays a role in the pathophysiology of diabetic nephropathy. An increase in the glomerular filtration rate (GFR) could result from primary actions at the glomerular/vascular level or could be the consequence of a primary increase in proximal tubular sodium reabsorption resulting in systemic volume expansion. Recently it was hypothesized that an increase in sodium reabsorption may lead to glomerular hyperfiltration through the tubulo-glomerular feedback mechanism (tubular-hypothesis) without volume expansion. We have studied 54 normoalbuminuric patients with type 1 diabetes. The GFR was measured by inulin clearance. Proximal and distal sodium reabsorption were calculated according to standard formulas using the free water clearance technique. Plasma volume, measured by the (125)I-albumin method, atrial natriuretic peptide (ANP) and the second messenger cyclic guanosine-3,5-monophosphate (c-GMP) were used as markers of extracellular volume expansion. Glomerular hyperfiltration (GFR >or= 130 mL min(-1) 1.73 m(-2)) was present in 14 out of 55 patients with diabetes (25%). There were no differences in plasma volume between normo-(NF) and hyper-filtrating (HF) patients (2933 +/- 423 in NF vs. 3026 +/- 562 mL in HF, NS). Also plasma ANP and c-GMP levels were not significantly different between the groups. The fractional proximal reabsorption of sodium was significantly increased in HF [fPRNa(+) (%) 90.1 +/- 2.0 vs. 91.5 +/- 1.6, P = 0.02]. There were no differences in distal sodium reabsorption or distal sodium load (approximately macula densa concentration of NaCl) in both groups. Our data suggest that the primary event in diabetic glomerular hyperfiltration is an increase in proximal tubular sodium reabsorption. They do not support the hypothesis that systemic volume expansion or ANP mediate glomerular hyperfiltration in patients with normoalbuminuric type 1 diabetes. As such, changes in tubular sodium handling most probably influence tubulo-glomerular feedback.

Hypophosphorémies d’origine génétique : avancées physiopathogéniques récentes

Renal proximal tubular reabsorption of phosphate and intestinal absorption both regulate phosphate homeostasis. Brush-border membrane Npt2a cotransporter is the key element in proximal tubular P (i) reabsorption. Inactivating mutations of Npt2a cause bone demineralisation and urolithiasis. An excess of a phosphaturic factor, called "Phosphatonin", could modulate phosphate reabsorption by inhibition on Npt2a. Inactivating mutation of PHEX, an endopeptidase-membrane coding gene, is responsible for X-linked Hypophosphatemia (XLH), because of an impaired degradation of phosphatonine by PHEX product. Autosomic Dominant Hypophosphatemic Rickets (ADHR) is explained by a mutation preventing FGF23 (one of the best identified phosphatonines) from cleavage. According recent data, FGF23, MEPE (Matrix Extracellular Phosphoglycoprotein) et FRP4 (frizzled related protein-4) are 3 putative "phosphatonines".

Temporal adaptation of tubuloglomerular feedback: Effects of COX-2

Reductions in proximal reabsorption cause increases in delivery of sodium chloride to the macula densa (MD), which activates the tubuloglomerular feedback (TGF) mechanism and reduces glomerular filtration rate. TGF undergoes temporal adaptation, permitting filtration rate to rise in spite of elevated MD delivery of NaCl. Inhibitors of nitric oxide synthase I (NOS I) prevent TGF adaptation, but angiotensin-converting enzyme inhibitors have no effect. COX-2 activity moves in parallel with changes in NOS I and intrarenal renin. We examined the impact of COX-2 inhibition on TGF temporal adaptation and effects of inhibition of COX-2 and NOS I on plasma and kidney angiotensin II (Ang II). Kidney blood flow (RBF) and glomerular filtration rate (GFR) were measured before and during benzolamide (BNZ) infusion in control Wistar rats and rats concurrently receiving COX-2 inhibitors. Plasma and kidney angiotensin II content was evaluated by radioimmunoassay in control rats, rats after 60 minutes of BNZ, and during COX-2 and NOS-1 inhibition after BNZ. BNZ reduced both RBF and GFR in all groups. During BNZ, RBF and GFR returned to normal control values within 60 minutes. COX-2 inhibitors totally prevented TGF adaptation. Plasma and kidney Ang II did not change after BNZ, and NOS I and COX-2 inhibitors had no effect on plasma or intrarenal Ang II. Within 1 hour after BNZ, rats undergo TGF temporal adaptation. Administration of COX-2 inhibitors prevented TGF temporal adaptation, identical to the effect of NOS I inhibition. Changes in intrarenal Ang II cannot explain this prevention of TGF temporal adaptation.

Pattern of Renal Function Recovery after Leptospirosis Acute Renal Failure

Background: Although acute renal failure (ARF) is a frequent complication of severe leptospirosis, there are few studies on renal function recovery in the literature. The objective of the present study was to verify how and when renal function recovery occurs after leptospirosis ARF. Patients and Methods: 35 patients with leptospirosis ARF (plasma creatinine [P_creat] ≧133 µmol/l at hospital admission) were prospectively studied during hospitalization, at discharge and 3 and 6 months after discharge. Creatinine clearance, fractional excretion of sodium and potassium, proteinuria and sodium proximal reabsorption were measured under normal sodium diet. Urinary pH and the ratio urinary to plasma osmolality (U/P_osm) were measured 18 h after food and water withdrawal. All parameters were also measured in 18 healthy volunteers. Presence of laboratorial alterations usually found in leptospirosis were evaluated in the patients. Patients were divided in 2 groups according to their maximum P_creat value during hospitalization: group 1 ( P_creat >442 µmol/l, n = 21), and group 2 (P_creat ≤442 µmol/l, n = 14). Results: All patients presented with jaundice, fever and myalgia. Bilirubin and creatine kinase were higher in group 1. Oliguria was observed in 11% of all patients and 49% required dialysis; all these patients were from group 1. All renal parameters were normal at the 6th month except U/P_osm that remained lower than normal. The pattern of renal function recovery was similar in both groups except for urinary volume. Conclusion: After leptospirosis ARF, renal function recovery is fast and complete after 6 months, except for urinary concentration capacity.

Compensation of proximal tubule malabsorption in AQP1-deficient mice without TGF-mediated reduction of GFR.

By crossing aquaporin 1 (AQP1)-/- and adenosine 1 receptor (A1AR)-/- mice, we generated an animal model that combines a proximal tubular absorption defect with absence of tubuloglomerular feedback (TGF) regulation of glomerular filtration rate (GFR). The aim of studies in these animals was to determine whether a TGF-induced reduction of GFR is a prerequisite for preventing potentially fatal fluid losses. In contrast to AQP1 deficient mice, AQP1/A1AR-/- mice were found to have a normal GFR. TGF responses were abolished in these animals, in contrast to AQP1-/- mice in which TGF responses of single nephron glomerular filtration rate (SNGFR) were left-shifted. Proximal tubule fluid absorption in AQP1/A1AR-/- mice was reduced to levels previously reported for AQP1-/- mice. However, SNGFR was significantly higher in AQP1/A1AR-/- than AQP1-/- mice (10.6 +/- 0.8 nL min(-1) vs. 5.9 +/- 0.7 nL min(-1)). As a consequence of the normal GFR and the reduced proximal reabsorption distal fluid delivery was markedly higher in the double knockout compared with normal or AQP1-/- mice (5.5 +/- 0.5 nL min(-1) vs. 2.35 +/- 0.3 nL min(-1) in AQP1-/-). Despite the approximate doubling of distal fluid and Cl delivery, AQP1/A1AR-/- mice have a normal salt excretion, normal arterial blood pressure, and only a small increase in plasma renin concentration. The ability to compensate for proximal tubule malabsorption without a TGF-induced reduction of GFR attests to a remarkable adaptability of distal tubule transport mechanisms.

Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats.

The present study investigated sodium balance and renal tubular function in cirrhotic rats with chronic blockade of the nitric oxide (NO) system. Rats were treated with the nonselective NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) starting on the day of common bile duct ligation (CBL). Three weeks of daily sodium balance studies showed that CBL rats developed sodium retention compared with sham-operated rats and that l-NAME treatment dose dependently deteriorated cumulative sodium balance by reducing urinary sodium excretion. Five weeks after CBL, renal clearance studies were performed, followed by Western blotting of the electroneutral type 3 sodium/proton exchanger (NHE3) and the Na-K-ATPase present in proximal tubules. Untreated CBL rats showed a decreased proximal reabsorption with a concomitant reduction of NHE3 and Na-K-ATPase levels, indicating that tubular segments distal to the proximal tubules were responsible for the increased sodium reabsorption. l-NAME-treated CBL rats showed an increased proximal reabsorption measured by the lithium clearance method and showed a marked increase in NHE3 and Na-K-ATPase protein levels. Our results show that chronic l-NAME treatment exacerbates the sodium retention found in CBL rats by a significant increase in proximal tubular reabsorption.

Lithium Transport in the Kidney of the Herring Gull Larus argentatus: Induction of Renal Li+Net Secretion by a Salt Loading

To find out whether salt loading can induce Li+ net secretion in the kidney of the birds that have an extrarenal organ (the salt gland) for excretion of NaCl excess (earlier, such effect was revealed in the pigeon and chicken, the birds that do not have the salt gland), the effect of intravenous NaCl injections (4–5 injections of 14–20 mmol/kg at 20–30-min intervals) on Li+ transport in the gull kidney was studied. Prior to the salt loading, above 99% of the filtered Li+ were reabsorbed in the kidney: fractional excretion of Li+ (FELi) was 0.0024 ± 0.0007 (mean ± SD), the Li+ reabsorption occurring not only in the proximal, but also in the distal tubule. Under conditions of the salt loading, two essentially different regimes of the kidney functioning were observed: net Li+ reabsorption (FELi = 0.63 ± 0.26) and net Li+ secretion (FELi = 1.26 ± 0.12). In the absence of the salt loading, Li+ (due to its distal reabsorption) does not fit requirements of an indicator of proximal reabsorption of Na+ and water. However, in the regimes of the “salt” net reabsorption and the “salt” net secretion, FELi probably can serve as an indicator of delivery of these substances to the end of the proximal tubule (the lithium clearance method). If this suggestion is correct, transition from the net Li+ reabsorption (FELi 1) with rise of the salt loading indicates the appearance of net Na+ secretion in the proximal tubule under these conditions. A comparison of the results for the gull and the chicken has shown that although the presence of the salt gland did not prevent transition of the kidney to the net Li+ secretion, its duration in the gull was significantly shorter. The comparative data are presented on parameters of renal function in the regimes of net Li+ secretion and net Li+ reabsorption. In both regimes, a linear correlation was observed between FELi and FENa; however, regression coefficients considerably differed. An abrupt break of the curve occurred at FELi ≈ 1.

Metabolic determinants of proximal sodium reabsorption in healthy women

Metabolic determinants of proximal sodium reabsorption in healthy women

Twenty-one years of developmental nephrology: the kidney then and now.

Developmental renal physiology was guided for a long time by the notion that the "immature" kidney is characterized by glomerular-tubular imbalance, with glomerular preponderance. In accordance with this concept, the filtering capacity of the developing kidney exceeds the ability of the renal tubules to handle the filtrate, resulting in the urinary loss of substances such as amino acids and bicarbonate. Estimates of age-related changes in glomerular volume, based on measurements of glomerular diameter, and of proximal tubular volume, based on measurements of tubular length and tubular diameter, appeared to support this contention. The experimental approach that led to these conclusions was based on the assumptions that the increase in glomerular size is distributed evenly between the vascular and nonvascular elements and that tubular volume increases pari passu with the luminal surface area. Both assumptions were proved wrong. Moreover, micropuncture studies performed in guinea pigs and rats revealed that the proportionality between glomerular filtration and proximal reabsorption of fluid (i.e., glomerulo-tubular balance) is maintained throughout development. Subsequent studies showed that several transport mechanisms function quite adequately from the first days of extrauterine life. Sodium is avidly reabsorbed in distal nephron segments, under the stimulus of the high levels of aldosterone present during infancy. The increase in the secretion of potassium that would occur in the adult under these circumstances is mitigated by the low expression of potassium channels. In the case of phosphate, there is enhanced reabsorption, particularly at the level of the proximal tubule, due in part to a growth-specific NaPi type II transporter. These different adaptive mechanisms converge towards the maintenance of a positive external balance for substances that are essential to growth. The emergence of cellular and molecular biology has also encouraged research in the field of renal morphology. The genes that control mesenchymal-epithelial interactions and the signaling factors that mediate their effect have been described. Progress is being made in the identification of genes involved in certain forms of renal malformations. Novel methods of investigation, such as DNA arrays, are likely to lead to an even fuller, dynamic portrayal of gene expression during nephrogenesis. Characterizing the functional correlates of these genes will require investigators who are not only proficient in molecular biology, but who are also masters of physiological methods.

Effect of Nitric Oxide Synthase Inhibition and Saline Administration on Blood Pressure and Renal Sodium Handling During Experimental Sepsis in Rats

Much effort has been made in recent years to clarify metabolic and renal function changes in sepsis. A number of studies performed in different models of sepsis have been described. One such model that is frequently used is cecal ligation and puncture (CLP) in rats. This model resembles human sepsis in several important aspects, such as an early phase of hyperdynamic, hypermetabolic sepsis followed by a late hypodynamic, hypometabolic phase. The present study evaluated the blood pressure (n = 5) and renal function changes during development of CLP renal failure and to determine the effects of NOS inhibition (L-NAME) and 0.15 M NaCl administration on tail blood pressure and renal function in randomly assigned five groups (n = 10 each): (1) Sham-operated, (2) Sham-operated L-NAME-treated, (3) CLP rats, (4) CLP L-NAME-treated, and (5) CLP 0.15 M NaCl-treated rats. The basal tail blood pressure was not significantly different among the four groups. One week later, arterial pressure was significantly increased in sham-operated L-NAME-treated rats (159 ± 12 mmHg) compared with the other groups (118 ± 9.0 mmHg in nontreated rats, p<0.05). Blood pressure shows a slightly and not significant decrease up to 12 h in L-NAME and 0.15 M NaCl treated rats, which in turn was followed by a significant reduced arterial pressure 18 h after CLP in both groups (L-NAME: 96.0 ± 3.6 mmHg, p<0.05) and NaCl: 82.3 ± 2.4 mmHg, p<0.05) compared to sham-operated groups. The glomerular filtration rate estimated by CCr decreases significantly in the CLP untreated group (p<0.001) and did not significantly differ from the sham-operated and L-NAME-treated groups (p = 0.4) during the studies of renal tubule sodium handling. On the other hand, subcutaneous 0.15 M NaCl administration prevented CCr decreases in CLP rats (p = 0.25). CLP increased the FENa in the sham-operated from: 857.2 ± 85.1 Δ% min−1 to CLP: 1197.8 ± 119.0 Δ% min−1. The high FENa to CLP was blunted and significantly reduced by previous systemic treatment of animals with L-NAME from sham-operated + L-NAME: 1368.0 ± 72.0 Δ% min−1 to CLP+L-NAME: 1148.0 ± 60.4 Δ% min−1 (p<0.01). The enhanced FENa in the CLP group were accompanied by a significant increase in proximal sodium reabsorption rejection. The salient findings of the present study suggest that a decrease in the blood pressure and creatinine clearance caused by CLP may benefit from L-NAME and fluid resuscitation during initial bacteremia (first 12 h) by promoting an additional increase of tubule sodium reabsorption in the post-proximal segments of nephrons, but these therapies could not prevent acute renal failure after established endotoxemia.

Hemodynamics of early tubuloglomerular feedback resetting during reduced proximal reabsorption

Carbonic anhydrase inhibition with benzolamide reduces proximal reabsorption and activates tubuloglomerular feedback (TGF). In rats, TGF activation for 30 to 60 minutes locally suppresses renin secretion and resets TGF rightward to accommodate increased late proximal flow. After 24 hours of TGF activation, there is upward resetting of GFR and increased activity of macula densa nitric oxide synthase I (NOS I). We studied renal hemodynamics during early TGF resetting with attention to the importance of renin suppression and NOS I activation. Left kidney blood flow (RBF, pulse Doppler) and glomerular filtration rate (GFR; inulin clearance or Fick method) were measured before and during benzolamide infusion (5 mg/kg bolus followed by 5 mg/kg/h IV) in Wistar rats concurrently receiving the converting enzyme inhibitor, enalaprilat (0.3 mg/kg/h IV) or NOS-I blocker S-methyl-thiocitrulline (SMTC; 2.7 mg/kg/h IV). Activating TGF initially reduced RBF and GFR in all groups as expected. During continuous benzolamide, RBF gradually increased toward baseline in control and enalaprilat-treated rats, but not in NOS I-blocked rats. After the initial decline, GFR did not change further during one hour of benzolamide in any group. During one hour of persistent TGF stimulation, RBF increases toward normal, but GFR does not. This requires an overall decrease in renal vascular resistance and a decrease in the ratio of efferent/afferent arteriolar resistance (RE/RA), implying a major decrease in RE. NOS I, but not angiotensin-converting enzyme (ACE), is required for RBF to increase during TGF resetting. Although the hemodynamic changes during TGF resetting resemble the response to blocking the renin-angiotensin system, these data fail to show that the increase in RBF during early TGF resetting is mediated by renin suppression.

Effect of mercury vapour exposure on urinary excretion of calcium, zinc and copper: relationship to alterations in functional and structural integrity of the kidney.

The kidney has a remarkable capacity to concentrate mercury (Hg) and as such is a primary target organ when exposure to Hg occurs, and it is also an organ for Hg excretion. The present work aims to investigate the effect of occupational Hg vapour exposure on the urinary excretion of calcium (Ca), zinc (Zn) and copper (Cu), and the possible association of this excretion to work duration as well as renal alterations. 83 non-smoker participants (36 referents, age: 35.6 +/- 9.5 years; 27 Hg vapour-exposed workers with < or = 10 years work duration, age: 33.0 +/- 5.1 years; and 20 Hg vapour-exposed workers with > or = 11 years work duration, age: 39.50 +/- 8.50 years) were included in the present study. Urinary levels of microalbumin (U-Malb) and retinol-binding protein (U-RBP) as well as cytosolic glutathione S-transferase activity (U-GST) were measured to assess the glomerular and proximal tubular reabsorption functions as well as structural integrity of proximal tubules; respectively. In addition, blood Hg (B-Hg), serum levels of Hg (S-Hg) and Ca (S-Ca), and urinary levels of Hg (U-Hg), Ca (U-Ca), Zn (U-Zn), Cu (U-Cu) and creatinine (U-cr) were estimated. In comparison to referents, all investigated parameters showed significant increase (except S-Ca and U-Zn/U-Cu ratio that significantly decreased among the workers as one group, S-Ca and U-Zn/U-Cu ratio that significantly and nonsignificantly decreased; respectively among workers with < or = 10 years work duration, S-Ca and U-Zn/U-Cu ratio that significantly decreased among workers with > or = 11 years work duration). In addition, B-Hg was nonsignificantly increased and S-Ca was significantly decreased; also, both U-Hg and U-Zn/U-Cu were nonsignificantly decreased among workers with > or = 11 years work duration in comparison to those with < or = 10 years work duration. Also, each of U-Hg, U-Ca, U-Zn and U-Cu was related to one another, while each of U-Ca, U-Zn and U-Cu was related to each of U-Malb, U-RBP and U-GST (except U-Zn was not related to U-GST). Hg vapour exposure leads to renal alterations which may parallel the change in proteinuria and enzymuria as well as the increased loss in urine of each of Ca, Zn and Cu. The urinary assessment of these metals may be used as a good indicator for renal dysfunction.