The effects of the inhibition of the renal carbonic anhydrase on the blood acid-base status in hypercapnic rats

Carbonic anhydrase 2 regulates acid-base homeostasis, and recent findings have indicated a correlation between cellular control of acid-base status and the innate defense of the kidney. Mice deficient in carbonic anhydrase 2 ( Car2−/− mice) have metabolic acidosis, impaired urine acidification, and are deficient in normal intercalated cells. The objective of the present study was to evaluate the biological consequences of carbonic anhydrase 2 deficiency in a murine model of pyelonephritis. Infection susceptibility and transcription of bacterial response components in Car2−/− mice were compared with wild-type littermate controls. Car2−/− mice had increased kidney bacterial burdens along with decreased renal bacterial clearance after inoculation compared with wild-type mice. Standardization of the urine pH and serum HCO3− levels did not substantially alter kidney infection susceptibility between wild-type and Car2−/− mice; thus, factors other than acid-base status are responsible. Car2−/− mice had significantly increased neutrophil-gelatinase-associated lipocalin mRNA and protein and expression at baseline and a marked decreased ability to upregulate key bacterial response genes during pyelonephritis. Our findings provide in vivo evidence that supports a role for carbonic anhydrase 2 and intercalated cells in promoting renal bacterial clearance. Decreased carbonic anhydrase expression results in increased antimicrobial peptide production by cells other than renal intercalated cells, which is not sufficient to prevent infection after a bacterial challenge.

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Renal regulation of acid-base balance in the bullfrog

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1961.201.6.980 ◽

1961 ◽

Vol 201 (6) ◽

pp. 980-986 ◽

Cited By ~ 15

Author(s):

Hisato Yoshimura ◽

Masateru Yata ◽

Minoru Yuasa ◽

Robert A. Wolbach

Keyword(s):

Carbonic Anhydrase ◽

Ammonia Excretion ◽

Respiratory Acidosis ◽

Acid Base Balance ◽

Acid Base ◽

Urinary Ph ◽

Base Balance ◽

Chloride Excretion ◽

Acid Load ◽

Renal Carbonic Anhydrase

Renal mechanisms for the maintenance of acid-base balance were studied in the normal bullfrog, during metabolic and respiratory acidosis, and after carbonic anhydrase inhibition. Following intravenous administration of 0.3–12 mmole HCl/ kg, as 0.1 n HCl, urinary pH (initially pH 6.3–7.7) did not change significantly. However, urinary ammonia excretion increased more than twofold, and within 3–5 days the cumulative increase was equivalent to the acid load given. Despite the increased ammonia excretion, chloride excretion did not increase after acid loading. In both normal and acidotic bullfrogs ammonia excretion was correlated with an increase in urinary pH. Respiratory acidosis in the small frog, Rana limnocharis, produced by exposure to 6.4% CO2 in air, induced neither urinary acidification nor increased ammonia excretion; both urinary sodium and bicarbonate excretion increased. When renal carbonic anhydrase was inhibited by acetazoleamide injection, urine flow, sodium excretion, and bicarbonate excretion increased markedly, urinary pH increased slightly, and urinary ammonia excretion remained unchanged. These renal responses to acidosis are compared with those of the acidotic dog.

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Carbonic anhydrase and proton secretion in turtle bladder mitochondrial-rich cells

AJP Renal Physiology ◽

10.1152/ajprenal.1991.260.3.f443 ◽

1991 ◽

Vol 260 (3) ◽

pp. F443-F458

Author(s):

C. Fritsche ◽

J. G. Kleinman ◽

J. L. Bain ◽

R. R. Heinen ◽

D. A. Riley

Keyword(s):

Carbonic Anhydrase ◽

Acid Base ◽

Proton Secretion ◽

Turtle Bladder ◽

Acid Base Status ◽

Reduced Density

Bladders from actively feeding turtles were processed for carbonic anhydrase (CA) cytochemically. CA-positive cells were identified as microplicated (MP) cells, microvillated (MV) cells, and subluminal (SL) cells. After acute enhancement of H+ secretion with 5% CO2, MP cells displayed extensive microplicae and a reduced density of apical subplasmalemmal vesicles, and they were CA reactive throughout a large part of the cytoplasm including the microplicae. After acute inhibition of H+ secretion with a pH 4.5 mucosal bath, CA staining was excluded from the microplicae and apical subplasmalemmal region of most MP cells, whereas microplicae varied from extensive to reduced, and subapical vesicle density remained elevated. MV cells were characterized by basolateral staining with sparing of the MV and apical subplasmalemmal region in all settings except 1) after 5% CO2 and 2) when MV cells were found in areas in which MP cells were stained to the lumen. These results indicate that CA is active at the site of H+ secretion in MP cells and is correlated with the acute acid-base status of the bladder.

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Renal acid-base physiology in marine teleost, the long-horned sculpin (Myoxocephalus octodecimspinosus)

AJP Renal Physiology ◽

10.1152/ajprenal.1992.263.1.f49 ◽

1992 ◽

Vol 263 (1) ◽

pp. F49-F55 ◽

Cited By ~ 7

Author(s):

T. H. Maren ◽

A. Fine ◽

E. R. Swenson ◽

D. Rothman

Keyword(s):

Carbonic Anhydrase ◽

Divalent Cations ◽

Marine Teleost ◽

Acid Base ◽

Titratable Acid ◽

Acid Load ◽

Renal Carbonic Anhydrase ◽

Ph Range ◽

Urinary Acid ◽

Very High

We have sought to define urinary acid-base excretion in the marine teleost using the long-horned sculpin, Myoxocephalus octodecimspinosus. Urine flow (1.7 ml.h-1.kg-1) is relatively high, and glomerular filtration rate is very low (2.9 ml.h-1.kg-1). The urine-to-plasma ratio of inulin is 2. Renal clearance of p-aminohippurate is very high (108 ml.h-1.kg-1); phosphate and divalent cations are also secreted. In this framework we found urinary pH to average 6.6, but infusion of acid or alkali elicited a pH range of 6.1-7.8. Untreated fish may also have alkaline urine; so it is not surprising that precipitates of calcium or magnesium phosphate are sometimes found in bladder. These are of fine sandy quality and never cause blockage. Infusion of buffer (imidazole) increased the concentration of titratable acid 11-fold and output 2.5-fold. Carbonic anhydrase inhibitors had no effect on any urinary component, and histochemical studies revealed that cytoplasm and membranes did not yield the specific cobalt stain for the enzyme. An alkaline load (NaHCO3) is rapidly dissipated by gill excretion, mediated in part by carbonic anhydrase. An acid load (HCl) is rapidly dissipated by gill excretion, not dependent on carbonic anhydrase, and some renal excretion. Comparison and contrast of the low rates of HCO3- reabsorption in the marine teleost (and elasmobranch) with those of mammals suggest strongly that renal carbonic anhydrase evolved in connection with these high reabsorptive rates beginning in freshwater fish and continuing through amphibia and birds.

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Roles of gill and red cell carbonic anhydrase in elasmobranch HCO3- and CO2 excretion

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1987.253.3.r450 ◽

1987 ◽

Vol 253 (3) ◽

pp. R450-R458 ◽

Cited By ~ 8

Author(s):

E. R. Swenson ◽

T. H. Maren

Keyword(s):

Carbonic Anhydrase ◽

Respiratory Acidosis ◽

Red Cell ◽

Acid Base ◽

Terrestrial Vertebrates ◽

Carbonic Anhydrase Inhibition ◽

Normal Metabolism ◽

Acid Base Status ◽

Erythrocyte Carbonic Anhydrase ◽

Co2 Elimination

We studied the roles of gill and erythrocyte carbonic anhydrase in normal CO2 transfer (metabolic CO2 elimination) and in HCO3- excretion during metabolic alkalosis in the resting and swimming dogfish shark, Squalus acanthias. Gill carbonic anhydrase was selectively inhibited (greater than 98.5%) by 1 mg/kg benzolamide, which caused no physiologically significant red cell carbonic anhydrase inhibition (approximately 40%). Enzyme in both tissues was inhibited by 30 mg/kg methazolamide (greater than 99%). Both drugs caused equivalent reductions in HCO3- excretion following an infusion of 9 mmol/kg NaHCO3 as measured by the rate of fall in plasma HCO3- and by transfer into seawater. Methazolamide (red cell and gill carbonic anhydrase inhibition) caused a respiratory acidosis in fish with normal acid-base status, whereas benzolamide (gill carbonic anhydrase inhibition) did not. The only effect observed with benzolamide in these fish was a small elevation in plasma HCO3-. These findings, taken together, suggest that red cell carbonic anhydrase is required for normal metabolic CO2 elimination by the gill. Although carbonic anhydrase is located in the respiratory epithelium, it appears to have no quantitative role in transfer of metabolic CO2 to the environment, a pattern similar to all terrestrial vertebrates. However, carbonic anhydrase in the gill is crucial to this organ's function in acid-base regulation, both in the excretion of H+ or HCO3- generated in normal metabolism and in various acid-base disturbances.

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Relative effects of carbonic anhydrase infusion or inhibition on carbon dioxide transport and acid-base status in the sea lamprey Petromyzon marinus following exercise

Journal of Experimental Biology ◽

10.1242/jeb.199.4.933 ◽

1996 ◽

Vol 199 (4) ◽

pp. 933-940

Author(s):

B Tufts ◽

S Currie ◽

J Kieffer

Keyword(s):

Carbon Dioxide ◽

Carbonic Anhydrase ◽

Venous Blood ◽

Extracellular Fluid ◽

Respiratory Acidosis ◽

Acid Base ◽

Carbon Dioxide Transport ◽

Co2 Transport ◽

Arterial Blood ◽

Acid Base Status

In vivo experiments were carried out to determine the relative effects of carbonic anhydrase (CA) infusion or inhibition on carbon dioxide (CO2) transport and acid-base status in the arterial and venous blood of sea lampreys recovering from exhaustive exercise. Infusion of CA into the extracellular fluid did not significantly affect CO2 transport or acid-base status in exercised lampreys. In contrast, infusion of the CA inhibitor acetazolamide resulted in a respiratory acidosis in the blood of recovering lampreys. In acetazolamide-treated lampreys, the post-exercise extracellular pH (pHe) of arterial blood was significantly lower than that in the saline-infused (control) lampreys. The calculated arterial and venous partial pressure of carbon dioxide (PCO2) and the total CO2 concentration in whole blood (CCO2wb) and red blood cells (CCO2rbc) during recovery in the acetazolamide-infused lampreys were also significantly greater than those values in the saline-infused control lampreys. These results suggest that the CO2 reactions in the extracellular compartment of lampreys may already be in equilibrium and that the access of plasma bicarbonate to CA is probably not the sole factor limiting CO2 transport in these animals. Furthermore, endogenous red blood cell CA clearly has an important role in CO2 transport in exercising lampreys.

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Effects of carbonic anhydrase inhibition on the acid base status in lamprey and trout

Respiration Physiology ◽

10.1016/0034-5687(94)00101-5 ◽

1995 ◽

Vol 99 (2) ◽

pp. 241-248 ◽

Cited By ~ 17

Author(s):

Raymond P. Henry ◽

Robert G. Boutilier ◽

Bruce L. Tufts

Keyword(s):

Carbonic Anhydrase ◽

Acid Base ◽

Carbonic Anhydrase Inhibition ◽

Acid Base Status

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Sodium, chloride, and bicarbonate movement from plasma to cerebrospinal fluid in cats

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1975.228.3.673 ◽

1975 ◽

Vol 228 (3) ◽

pp. 673-683 ◽

Cited By ~ 57

Author(s):

BP Vogh ◽

TH Maren

Keyword(s):

Cerebrospinal Fluid ◽

Carbonic Anhydrase ◽

Choroid Plexus ◽

Rate Constants ◽

Secretory Cells ◽

Acid Base ◽

Rapid Exchange ◽

Primary Signal ◽

Carbonic Anhydrase Inhibition ◽

Acid Base Status

Rate constants have been determined for the entry of 22Na+, 36Cl minus, and H14CO3- into CSF from plasma in cats during changes in Pco2 with and without inhibition of carbonic anhydrase. The application of these rate constants to movement of unlabeled electrolytes suggests that Na+ and Cl minus enter CSF by a one-way flux into newly formed fluid, but that entering HCO3-is involved both in net accumulation in new fluid and in rapid exchange with existing HCO3-. The entering HCO3-ions are not transferred from plasma but are formed in secretory cells from dissolved CO2. The exchange component of HCO3-entry is Pco2-dependent; entry of Na+ and Cl minus is not; hence net rate of HCO3-formation estimated by difference between Na+ and Cl minus is not Pco2 dependent. The net rate of HCO3-formation lies within the availability of CO2 from blood flow to choroid plexus but is not necessarily limited to this tissue. When carbonic anhydrase is inhibited, the net rate of formation of HCO3-is close to the calculated uncatalyzed rate expected for choroid plexus. The entry of all three ions is reduced by carbonic anhydrase inhibition, but the enzyme does not seem to provide the primary signal for alteration of CSF acid-base status. Regulation of CSF pH appears to be achieved through changes in HCO3-concentration that occur subsequent to the secretion of HCO3--rich new fluid.

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To Manage Infantile Hypertrophic Pyloric Stenosis by "Double-Y Pyloromyotomy" is a better Surgical Approach

Journal of Paediatric Surgeons of Bangladesh ◽

10.3329/jpsb.v1i2.19532 ◽

2014 ◽

Vol 1 (2) ◽

pp. 143-147

Author(s):

Md. Ansar Ali ◽

Kaniz Hasina ◽

Shahnoor Islam ◽

Md. Ashraf Ul Huq ◽

Md. Mahbub-Ul Alam ◽

...

Keyword(s):

Weight Gain ◽

Pyloric Stenosis ◽

Hypertrophic Pyloric Stenosis ◽

Treatment Modalities ◽

Infantile Hypertrophic Pyloric Stenosis ◽

Postoperative Vomiting ◽

Acid Base ◽

Feeding Regimes ◽

Acid Base Status ◽

Postoperative Feeding

Background: Different treatment modalities and procedures have been tried for the management of infantile hypertrophic pyloric stenosis. But surgery remains the mainstay for management of IHPS. Ramstedts pyloromyotomy was described almost over a hundred years ago and to date remains the surgical technique of choice. An alternative and better technique is the double-Y pyloromyotomy, which offer better results for management of this common condition.Methods: A prospective comparative interventional study of 40 patients with IHPS was carried out over a period of 2 years from July 2008 to July 2010. The patients were divided into 2 equal groups of 20 patients in each. The study was designed that all patients selected for study were optimized preoperatively regarding to hydration, acid-base status and electrolytes imbalance. All surgeries were performed after obtaining informed consent. Standard preoperative preparation and postoperative feeding regimes were used. The patients were operated on an alternate basis, i.e., one patient by Double-Y Pyloromyotomy(DY) and the next by aRamstedts Pyloromyotomy (RP). Data on patient demographics, operative time, anesthesia complications, postoperative complications including vomiting and weight gain were collected. Patients were followed up for a period of 3 months postoperatively. Statistical assessments were done by using t test.Results: From July 2008 through July 2010, fourty patients were finally analyzed for this study. Any statistical differences were observed in patient population regarding age, sex, weight at presentation, symptoms and clinical condition including electrolytes imbalance and acid-base status were recorded. Significant differences were found in postoperative vomiting and weight gain. Data of post operative vomiting and weight gain in both groups were collected. Vomiting in double-Y(DY) pyloromyotomy group (1.21 ± 0.45days) vs Ramstedts pyloromyotomy (RP) group(3.03 ± 0.37days) p= 0.0001.Weight gain after 1st 10 days DY vs RP is ( 298 ± 57.94 gm vs193±19.8 gm p=0.0014), after 1 month (676.67±149.84 gm vs 466.67 ± 127.71 gm, p=0.0001), after 2months (741.33± 278.74 gm vs 490±80.62 gm, p=0.002) and after 3 months (582±36.01gm vs 453.33±51.64 gm, p=0.0001).No long-term complications were reported and no re-do yloromyotomy was needed.Conclusion: The double-Y pyloromyotomy seems to be a better technique for the surgical management of IHPS. It may offer a better functional outcome in term of postoperative vomiting and weight gain.DOI: http://dx.doi.org/10.3329/jpsb.v1i2.19532

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