Respiratory acidosis in carbonic anhydrase II-deficient mice

Lien, Yeong‐Hau H.; Lai, Li‐Wen

doi:10.1152/ajplung.1998.274.2.l301

Cited by 29 publications

(29 citation statements)

References 24 publications

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“…This modulation has been described in nuclear processes, but the same rationale could be applied to other cAMP-mediated process (32) and HCO 3 Ϫ /CO 2 is a well recognized physiologic buffer system. Also, carbonic anhydrase, which is expressed in alveolar epithelial cells, could participate because of its action in CO 2 hydration and alveolar elimination (33,34).…”

Section: Discussionmentioning

confidence: 99%

Hypocapnic but Not Metabolic Alkalosis Impairs Alveolar Fluid Reabsorption

Myrianthefs

Briva

Lecuona

et al. 2005

Am J Respir Crit Care Med

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Acid-base disturbances, such as metabolic or respiratory alkalosis, are relatively common in critically ill patients. We examined the effects of alkalosis (hypocapnic or metabolic alkalosis) on alveolar fluid reabsorption in the isolated and continuously perfused rat lung model. We found that alveolar fluid reabsorption after 1 hour was impaired by low levels of CO 2 partial pressure (PCO 2 ; 10 and 20 mm Hg) independent of pH levels (7.7 or 7.4). In addition, PCO 2 higher than 30 mm Hg or metabolic alkalosis did not have an effect on this process. The hypocapnia-mediated decrease of alveolar fluid reabsorption was associated with decreased Na,K-ATPase activity and protein abundance at the basolateral membranes of distal airspaces. The effect of low PCO 2 on alveolar fluid reabsorption was reversible because clearance normalized after correcting the PCO 2 back to normal levels. These data suggest that hypocapnic but not metabolic alkalosis impairs alveolar fluid reabsorption. Conceivably, correction of hypocapnic alkalosis in critically ill patients may contribute to the normalization of lung ability to clear edema.Keywords: alveolar epithelial cells; hypocapnic alkalosis; ion transport; Na,K-ATPase; pulmonary edemaThe resolution of pulmonary edema is the result of active sodium transport across the alveolar epithelium (1-5). Sodium enters the alveolar epithelial cells via apically located sodium channels, and it is extruded via basolaterally located sodium pumps (Na, K-ATPases), which causes water to be reabsorbed from the alveolar space (4, 6-10). In experimental models, it has been reported that alveolar fluid reabsorption (AFR) is decreased during acute hyperoxia (11), hypoxia (12), ventilator-associated lung injury (13), increased left atrial pressures (14), infection (15), and scorpion envenomation (16). In some of these models of lung injury, the impairment in AFR has been associated with decreased Na,K-ATPase activity and protein abundance at the basolateral membrane of alveolar epithelial cells (13,(16)(17)(18).Acid-base disturbances and particularly hypocapnia can be observed during hyperventilation because it may occur during air travel, hiking at high altitudes, early asthma attack, diabetic ketoacidosis, or systemic inflammatory response syndrome (19)(20)(21)(22). The effect of hypocapnic alkalosis on alveolar fluid reabsorption as an index of alveolar epithelial function has not been eluci- dated. However, it has been reported that when AFR is impaired in patients with lung dysfunction, it is associated with worst outcomes (23).The present study examined the effects of hypocapnic alkalosis by changing the levels of CO 2 in the pulmonary circulation of the isolated, perfused, fluid-filled rat lung model. In parallel experiments, we examined the effects of CO 2 partial pressure (Pco 2 ) changes on Na,K-ATPase activity and protein abundance at the plasma membranes of distal airspaces. METHODSPathogen-free male Sprague-Dawley rats weighing 320 to 350 g were purchased from Harlan Sprague Dawley (Indiana...

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Section: Discussionmentioning

confidence: 99%

Hypocapnic but Not Metabolic Alkalosis Impairs Alveolar Fluid Reabsorption

Myrianthefs

Briva

Lecuona

et al. 2005

Am J Respir Crit Care Med

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“…Mice lacking CA II showed respiratory acidosis, as reported in ref. 25. This phenomenon is explained by the fact that CA II plays an important role in CO 2 exchange by erythrocytes.…”

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confidence: 97%

Carbonic anhydrase isozyme-II-deficient mice lack the duodenal bicarbonate secretory response to prostaglandin E ₂

Leppilampi

Parkkila²,

Karttunen³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Duodenal bicarbonate secretion (DBS) is accepted as the primary mucosal defense against acid discharged from the stomach and is impaired in patients with duodenal ulcer disease. The secretory response to luminal acid is the main physiological stimulus for DBS and involves mediation by PGE 2 produced by mucosal cells. The aim of this investigation is to elucidate the role of carbonic anhydrases (CAs) II and IX in PGE 2-mediated bicarbonate secretion in the murine duodenum. CA II-and IX-deficient mice and different combinations of their heterozygous and WT counterparts were studied. A 10-mm segment of the proximal duodenum with intact blood supply was isolated, and DBS was titrated by pH-stat (TitroLine-easy, Schott, Mainz, Germany). Mean arterial blood pressure (MAP) was continuously recorded, and blood acid͞base balance and gastrointestinal morphology were analyzed. The duodenal segment spontaneously secreted HCO 3 ؊ at a steady basal rate of 5.3 ؎ 0.6 mol⅐cm ؊1 ⅐h ؊1 . Perfusing the duodenal lumen for 20 min with 47 M PGE2 caused a significant increase in DBS to 13.0 ؎ 2.9 mol⅐cm ؊1 ⅐h ؊1 , P < 0.0001. The DBS response to PGE2 was completely absent in Car2 ؊/؊ mice, whereas basal DBS was normal. The CA IX-deficient mice with normal Car2 alleles showed a slight increase in DBS. Histological abnormalities were observed in the gastroduodenal epithelium in both CA II-and IX-deficient mice. Our data demonstrate a gastrointestinal phenotypic abnormality associated with CA II deficiency. The results show that the stimulatory effect of the duodenal secretagogue PGE 2 completely depends on CA II. duodenal mucosal protection ͉ gastroduodenal histological abnormalities ͉ gastrointestinal phenotype

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“…Using an in vitro lung model and the CAII inhibitor, acetazolamide, Crandall and O'Brasky first demonstrated the role that CAII plays in CO 2 elimination by the lungs (5). CAII-deficient mice have been reported to develop respiratory acidosis as a consequence of CO 2 retention in the lungs (6).…”

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confidence: 99%

Carbonic Anhydrase II and Alveolar Fluid Reabsorption during Hypercapnia

Chen¹,

Lecuona²,

Briva³

et al. 2008

Am J Respir Cell Mol Biol

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IllinoisCarbonic anhydrase II (CAII) plays an important role in carbon dioxide metabolism and intracellular pH regulation. In this study, we provide evidence that CAII is expressed in both type I (AECI) and type II (AECII) alveolar epithelial cells by RT-PCR and Western blotting in freshly isolated rat cells. These results were further confirmed by double immunostaining with CAII antibodies and AECI-or AECII-specific markers in freshly isolated alveolar epithelial cells and rat lung tissues. Inhibition of CAII by acetazolamide or methazolamide delayed the decrease in the intracellular pH observed during hypercapnia in cultured AECI, AECII, and AECI-like cells. In an isolated-perfused rat lung model, alveolar fluid reabsorption significantly decreased during high CO 2 exposure, which was not prevented by carbonic anhydrase inhibition. Thus, we provide evidence that CAII is expressed in rat alveolar epithelial cells and does not regulate lung alveolar fluid reabsorption during hypercapnia.

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Respiratory acidosis in carbonic anhydrase II-deficient mice

Cited by 29 publications

References 24 publications

Hypocapnic but Not Metabolic Alkalosis Impairs Alveolar Fluid Reabsorption

Hypocapnic but Not Metabolic Alkalosis Impairs Alveolar Fluid Reabsorption

Carbonic anhydrase isozyme-II-deficient mice lack the duodenal bicarbonate secretory response to prostaglandin E ₂

Carbonic Anhydrase II and Alveolar Fluid Reabsorption during Hypercapnia

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Respiratory acidosis in carbonic anhydrase II-deficient mice

Cited by 29 publications

References 24 publications

Hypocapnic but Not Metabolic Alkalosis Impairs Alveolar Fluid Reabsorption

Hypocapnic but Not Metabolic Alkalosis Impairs Alveolar Fluid Reabsorption

Carbonic anhydrase isozyme-II-deficient mice lack the duodenal bicarbonate secretory response to prostaglandin E 2

Carbonic Anhydrase II and Alveolar Fluid Reabsorption during Hypercapnia

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Carbonic anhydrase isozyme-II-deficient mice lack the duodenal bicarbonate secretory response to prostaglandin E ₂