Ammoniagenesis by the Isolated Perfused Rat Kidney: The Critical Role of Urinary Acidification

1979 ◽  
Vol 56 (4) ◽  
pp. 353-364 ◽  
Author(s):  
R. L. Tannen ◽  
B. D. Ross
Keyword(s):  
Metabolic Acidosis ◽  
Rat Kidney ◽  
Critical Role ◽  
Sodium Reabsorption ◽  
Ammonia Production ◽  
Bicarbonate Concentration ◽  
Urine Ph ◽  
Average Value ◽  
Acute Metabolic Acidosis

1. The effect of metabolic acidosis simulated in vitro on ammoniagenesis was investigated by using the isolated kidney of the rat perfused with an albumin Krebs—Henseleit medium containing glutamine and glucose. 2. Addition of HCl to a perfusate of normal bicarbonate concentration resulted in a prompt increase in urine flow rate, decrease in fractional sodium reabsorption and decrease in urine pH. 3. A minimum urine pH as low as 5·15 was achieved, with an average value of 5·92, indicating that this preparation has the capacity to acidify normally. 4. In contrast with studies in vitro with other preparations, with the functional perfused kidney a diminution in perfusate bicarbonate concentration resulted in a prompt increase in ammonia production, which was strikingly correlated with the decrease in urine pH. 5. The increase in ammonia production was diminished in studies carried out with a non-urinating kidney, in comparison with those that exhibited significant urine acidification. 6. These data suggest that a decrease in urine pH with trapping of ammonia in the urine may be a critical stimulus for increased ammonia production in acute metabolic acidosis.

Net proton influx into bone during metabolic, but not respiratory, acidosis

1988 ◽  
Vol 254 (3) ◽  
pp. F306-F310 ◽  
Author(s):  
D. A. Bushinsky
Keyword(s):  
Metabolic Acidosis ◽  
Bone Mineral ◽  
Respiratory Acidosis ◽  
Mineral Dissolution ◽  
Calcium Efflux ◽  
Bicarbonate Concentration ◽  
Medium Ph ◽  
Acute Metabolic Acidosis ◽  
Initial Medium

During acute metabolic acidosis there is a net influx of protons into bone, decreasing the elevated proton concentration. Whether there is an influx of protons into bone during acute respiratory acidosis is not known. To determine the effect of respiratory acidosis on net proton flux (JH) relative to bone, we compared JH from neonatal mouse calvariae incubated for 3 h in medium acidified by an increase in PCO2 (respiratory acidosis) with that from calvariae incubated in medium acidified to the same extent by a decrease in bicarbonate concentration (metabolic acidosis). The initial medium pH with respiratory acidosis was not different from that with metabolic acidosis (7.108 +/- 0.005 vs. 7.091 +/- 0.007, respectively, P = NS). During respiratory acidosis there was no JH from bone relative to the medium (JH = 236 +/- 93 neq.bone-1.3h-1, P = NS vs. 0); however, during metabolic acidosis there was net proton influx from the medium into bone (JH = -703 +/- 108, P less than 0.05 vs. 0, P less than 0.001 vs. respiratory acidosis). There was less calcium efflux from bone during respiratory than during metabolic acidosis (JCa = 68 +/- 6 nmol.bone-1.3 h-1 vs. 100 +/- 9, respectively, P less than 0.001). There is a net influx of protons into bone in vitro during acute metabolic, but not during acute respiratory, acidosis. The smaller calcium efflux during respiratory acidosis may indicate less net bone mineral dissolution and thus less buffer release into the medium.

Effect of Decrease in Bicarbonate Concentration on Metabolism of the Isolated Perfused Rat Kidney

1979 ◽  
Vol 57 (1) ◽  
pp. 103-111 ◽  
Author(s):  
B. D. Ross ◽  
R. L. Tannen
Keyword(s):  
Metabolic Acidosis ◽  
Metabolic Regulation ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Rat Kidney ◽  
Ammonia Production ◽  
Perfusion Medium ◽  
Isolated Perfused Rat Kidney ◽  
Acid Urine ◽  
Perfused Rat Kidney ◽  
Acute Metabolic Acidosis

1. An isolated perfused rat kidney preparation which responds to acidification of the perfusion medium with the production of an acid urine and increased ammonia production was used to study the metabolic regulation of ammonia production from glutamine. 2. An inhibitor of gluconeogenesis at phosphoenolpyruvate carboxykinase(GTP), mercaptopicolinate, completely prevented the increase in ammoniagenesis, without preventing acidification of the urine. 3. Acidification of the perfusion medium from pH 7·4 to 7·0 reduced the renal concentrations of malate and 2-oxoglutarate. 4. Malate concentration was restored by inhibition of phosphoenolpyruvate carboxykinase(GTP), but 2-oxoglutarate content remained low. This indicates that accelerated gluconeogenesis in acute acidosis cannot be the explanation for the fall in 2-oxoglutarate concentration. 5. The fall in 2-oxoglutarate content is taken to indicate an important fall in tissue pH or in the redox ratio (NAD+/NADH) or both during acute metabolic acidosis. 6. From these studies with lowered bicarbonate two separate stimuli to ammoniagenesis in acute metabolic acidosis are postulated: urinary trapping of ammonia and increased disposal of glutamine carbon atoms via the pathway of glucose synthesis.

Adaptive changes in renal acidification in response to chronic respiratory acidosis

1985 ◽  
Vol 248 (4) ◽  
pp. F492-F499 ◽  
Author(s):  
R. L. Tannen ◽  
B. Hamid
Keyword(s):  
Metabolic Acidosis ◽  
Proton Transport ◽  
Respiratory Acidosis ◽  
Hydrogen Ion ◽  
Distal Nephron ◽  
Urine Ph ◽  
Chronic Metabolic Acidosis ◽  
Adaptive Changes ◽  
Secretory Capacity

To examine whether chronic respiratory acidosis results in adaptive changes in renal acidification, rats were housed for 3 days in an environmental chamber with an ambient CO2 content of 10% and their kidneys were perfused in vitro according to two protocols. To assess hydrogen ion secretory capacity of the distal nephron, perfusions were carried out with a low bicarbonate concentration, in the absence of ammoniagenic substrate, and with saturating quantities of the buffer creatinine. Under these conditions, the titration of creatinine at a pH less than 6.0 (TA pH 6.0) reflects the H+ secretory capacity of a discrete functional segment of the distal nephron. Kidneys from rats with chronic respiratory acidosis exhibited a significantly lower urine pH and higher rate of TA pH 6.0 than controls perfused in this fashion, indicative of an adaptive increase in the distal nephron capacity for proton transport. This adaptation was comparable with that reported previously for rats exposed to chronic metabolic acidosis. Furthermore, evidence of adaptation persisted in the presence of amiloride (10(-5) M), suggesting that it reflects, at least in part, a sodium-independent mechanism of proton transport. Hydrogen ion secretion by the proximal nephron was assessed by performing standard bicarbonate titration curves with kidneys from rats with chronic respiratory acidosis, chronic metabolic acidosis, and controls using a perfusate equilibrated with 95% O2/5% CO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Bicarbonate: The Alternative Buffer for Peritoneal Dialysis

1996 ◽  
Vol 16 (1_suppl) ◽  
pp. 109-113 ◽  
Author(s):  
Jutta Passlick-Deetjen ◽  
Judith Kirchgessner
Keyword(s):  
Peritoneal Dialysis ◽  
Metabolic Acidosis ◽  
Cell Function ◽  
Multicenter Trial ◽  
The Body ◽  
Bicarbonate Concentration ◽  
Promising Alternative ◽  
Technical Problems ◽  
Cell Functions

For a long time bicarbonate, the physiological buffer of the body, was suggested to be the best buffer for peritoneal dialysis. However, since the production of bicarbonate containing solutions is associated with technical problems, lactate was favored. To avoid the well-known disadvantages of lactate solution concerning biocompatibility and possible metabolic side effects, different attempts have been made to use bicarbonate as a buffer in peritoneal dialysis. One of the major approaches was the total replacement of lactate by bicarbonate combined with storage of the fluid in a specially designed double-chamber bag. Further solutions of the above-mentioned problem were the on-line preparation of bicarbonate fluids for intermittent peritoneal dialysis, the addition of bicarbonate just before use, the combination of bicarbonate with organic acids, or its combination with the dipeptide glycylglycine as a stabilizing agent. By now, the beneficial effect of the neutral bicarbonate fluid, for example, on cell viability and cell functions, has been demonstrated in many different in vitro and animal studies. However, only few reports on clinical experience have been published. These investigations demonstrated independently that bicarbonate fluids diminish inflow pain, are well tolerated by the patients, and may correct metabolic acidosis of uremic patients. A controlled randomized multicenter trial using 34 mmol/L bicarbonate for at least three months confirmed that bicarbonate is as efficacious as lactate in equimolar concentrations. Concomitant investigations on energy metabolism and redox state of red blood cells and phospholipid secretion of mesothelial cells additionally demonstrated the improvement of cell function with bicarbonate solutions. For some patients with severe metabolic acidosis the bicarbonate concentration used in the multicenter trial seemed to be too low. Thus, a fluid containing a higher bicarbonate concentration was tested in a pilot study resulting in the expected significant increase of arterial bicarbonate levels. In summary, bicarbonate-containing peritoneal dialysis solutions are a promising alternative to lactate, especially if bicarbonate concentrations are adjusted individually to the patient's need.

Importance of medullary events in ammonium excretion: studies in acute respiratory and acute metabolic acidosis

1983 ◽  
Vol 61 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Andre Gougoux ◽  
Patrick Vinay ◽  
Guy Lemieux ◽  
Marc Goldstein ◽  
Bobby Stinebaugh ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Collecting Duct ◽  
Respiratory Acidosis ◽  
Renal Medulla ◽  
Hydrogen Ion ◽  
Ammonium Excretion ◽  
Urine Ph ◽  
Ion Secretion ◽  
Medullary Collecting Duct ◽  
Acute Metabolic Acidosis

The renal medulla can play an important role in acid excretion by modulating both hydrogen ion secretion in the medullary collecting duct and the medullary [Formula: see text]. The purpose of these experiments was to characterize the intrarenal events associated with ammonium excretion in acute acidosis. Cortical events were monitored in two ways: first, the rates of glutamine extraction and ammoniagenesis were assessed by measuring arteriovenous differences and the rate of renal blood flow; second, the biochemical response of the ammoniagenesis pathway was examined by measuring glutamate and 2-oxoglutarate, key renal cortical metabolites in this pathway. There were no significant differences noted in any of these cortical parameters between acute respiratory and metabolic acidosis. Despite a comparable twofold rise in ammonium excretion in both cases, the urine pH, [Formula: see text], and the urine minus blood [Formula: see text] difference (U-B [Formula: see text]) were lower during acute hypercapnia. In these experiments, the urine [Formula: see text] was 34 mmHg (1 mmHg = 133.322 Pa) lower than that of the blood during acute respiratory acidosis while the U-B [Formula: see text] was 5 ± 3 mmHg in acute metabolic acidosis. Thus there were significant differences in medullary events during these two conditions. Although the urine pH is critical in determining ammonium excretion in certain circumstances, these results suggest that regional variations in the medullary [Formula: see text] can modify this relationship.

scholarly journals Galectin-3 mediates oligomerization of secreted hensin using its carbohydrate-recognition domain

2013 ◽  
Vol 305 (1) ◽  
pp. F90-F99 ◽  
Author(s):  
Soundarapandian Vijayakumar ◽  
Hu Peng ◽  
George J. Schwartz
Keyword(s):  
Metabolic Acidosis ◽  
Collecting Duct ◽  
Critical Role ◽  
Rabbit Kidney ◽  
Intercalated Cells ◽  
Carbohydrate Recognition ◽  
Terminal Domain ◽  
Galectin 3 ◽  
Number Of Cells

A multidomain, multifunctional 230-kDa extracellular matrix (ECM) protein, hensin, regulates the adaptation of rabbit kidney to metabolic acidosis by remodeling collecting duct intercalated cells. Conditional deletion of hensin in intercalated cells of the mouse kidney leads to distal renal tubular acidosis and to a significant reduction in the number of cells expressing the basolateral chloride-bicarbonate exchanger kAE1, a characteristic marker of α-intercalated cells. Although hensin is secreted as a monomer, its polymerization and ECM assembly are essential for its role in the adaptation of the kidney to metabolic acidosis. Galectin-3, a unique lectin with specific affinity for β-galactoside glycoconjugates, directly interacts with hensin. Acidotic rabbits had a significant increase in the number of cells expressing galectin-3 in the collecting duct and exhibited colocalization of galectin-3 with hensin in the ECM of microdissected tubules. In this study, we confirmed the increased expression of galectin-3 in acidotic rabbit kidneys by real-time RT-PCR. Galectin-3 interacted with hensin in vitro via its carbohydrate-binding COOH-terminal domain, and the interaction was competitively inhibited by lactose, removal of the COOH-terminal domain of galectin-3, and deglycosylation of hensin. Galectin-9, a lectin with two carbohydrate-recognition domains, is also present in the rabbit kidney; galectin-9 partially oligomerized hensin in vitro. Our results demonstrate that galectin-3 plays a critical role in hensin ECM assembly by oligomerizing secreted monomeric hensin. Both the NH2-terminal and COOH-terminal domains are required for this function. We suggest that in the case of galectin-3-null mice galectin-9 may partially substitute for the function of galectin-3.

Adaptive redistribution of NBCe1-A and NBCe1-B in rat kidney proximal tubule and striated ducts of salivary glands during acid-base disturbances

2007 ◽  
Vol 293 (6) ◽  
pp. R2400-R2411 ◽  
Author(s):  
Alena Brandes ◽  
Oliver Oehlke ◽  
Anne Schümann ◽  
Stefanie Heidrich ◽  
Frank Thévenod ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Rat Kidney ◽  
Posttranslational Regulation ◽  
Acid Base ◽  
Duct Cells ◽  
Wistar Kyoto ◽  
Acute Metabolic Acidosis ◽  
Immortalized Cell

The cellular distribution of the NH2-terminal electrogenic Na+-HCO3− cotransporter (NBCe1) variants NBCe1-A and NBCe1-B has been investigated in rat kidney and submandibular gland (SMG) under physiological conditions and after systemic acid-base perturbations. Moreover, the in vivo data were complemented in vitro by using an immortalized cell line derived from the S1 segment of the proximal tubule (PT) of normotensive Wistar-Kyoto rats (WKPT-0293 Cl.2). NBCe1-A was basolaterally localized in PT cells, whereas NBCe1-B exhibited intracellular and basolateral distribution. SMG showed transcript and protein expression for NBCe1-A and NBCe1-B. NBCe1-B was basolaterally localized in duct cells; NBCe1-A was found intracellularly in salivary striated ducts and apically in main duct cells. Acute metabolic acidosis significantly increased cells that showed basolateral NBCe1-A in the PT, indicating increased HCO3− reabsorption, and significantly decreased cells that exhibited basolateral NBCe1-B in the salivary ducts, suggesting decreased HCO3− secretion. Chronic acidosis had no effect on NBCe1 distribution in PT but significantly increased the percentage of cells with basolateral NBCe1-A in salivary striated duct cells, suggesting increased HCO3− reabsorption. In contrast, chronic alkalosis caused adaptive redistribution of NBCe1-A and NBCe1-B in renal PT, favoring decreased HCO3− reabsorption. In vitro, WKPT-0293 Cl.2 cells expressed key acid-base transporters. Extracellular alkalosis downregulated NBCe1-A protein. WKPT-0293 Cl.2 cells are therefore a useful model to study renal acid-base regulation in vitro. The results propose redistribution of the transporters as a potential posttranslational regulation modus during acid-base disturbances. Moreover, the data demonstrate that renal PT and salivary duct epithelia respond to acid-base disturbances by an opposite redistribution pattern for NBCe1-A and NBCe1-B, reflecting specialized functions as the HCO3−-reabsorbing and HCO3−-secreting epithelium, respectively.

Sodium-dependent bicarbonate absorption by cortical thick ascending limb of rat kidney

1985 ◽  
Vol 248 (6) ◽  
pp. F821-F829 ◽  
Author(s):  
D. W. Good
Keyword(s):  
Hydrogen Exchange ◽  
Apical Membrane ◽  
Rat Kidney ◽  
Carbonic Anhydrase Activity ◽  
Detectable Effect ◽  
Thick Ascending Limb ◽  
Bicarbonate Concentration ◽  
Sodium Dependent ◽  
Transepithelial Voltage

In vitro microperfusion experiments were performed to investigate the mechanism of bicarbonate absorption in the cortical thick ascending limb of the rat. Tubules were perfused at 1.0-1.5 nl X min-1 X mm-1 and bicarbonate concentration was 25 mM in the perfusate and bath. Bicarbonate absorption rates were determined by microcalorimetry. Control tubules absorbed bicarbonate at a mean rate of 9.5 +/- 0.6 pmol X min-1 X mm-1. The limiting luminal bicarbonate concentration was approximately 5 mM for tubules perfused at slow rates with 25 mM bicarbonate in the bath. Acetazolamide (10(-4)M) in the bath reduced bicarbonate absorption by 76% without significant effect on transepithelial voltage. Removing sodium from the perfusate and bath or removing potassium from the bath reduced bicarbonate absorption and transepithelial voltage to near zero. Adding amiloride (5 X 10(-4) or 10(-3) M) to the perfusate reduced bicarbonate absorption by 60-75% without detectable effect on transepithelial voltage. Adding furosemide (10(-4)M) to the perfusate increased bicarbonate absorption significantly by 40-50% while decreasing transepithelial voltage from 17 to 1.8 mV. Thus, bicarbonate absorption by cortical thick ascending limbs requires carbonic anhydrase activity and sodium transport but is not dependent on transepithelial voltage. When considered together, the results are consistent with mediation of the bicarbonate absorption by apical membrane sodium-hydrogen exchange.

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