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

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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The distribution of branchial carbonic anhydrase and the effects of gill and erythrocyte carbonic anhydrase inhibition in the channel catfish Ictalurus punctatus

Journal of Experimental Biology ◽

10.1242/jeb.134.1.201 ◽

1988 ◽

Vol 134 (1) ◽

pp. 201-218 ◽

Cited By ~ 6

Author(s):

R. P. Henry ◽

N. J. Smatresk ◽

J. N. Cameron

Keyword(s):

Carbonic Anhydrase ◽

Ictalurus Punctatus ◽

Channel Catfish ◽

Time Course ◽

Respiratory Acidosis ◽

Transport Processes ◽

Delay Compensation ◽

Acid Base ◽

Acid Base Disturbance ◽

Erythrocyte Carbonic Anhydrase

Carbonic anhydrase (CA) activity was assayed in lysed erythrocytes and in branchial cytoplasm, mitochondria and microsomes of the channel catfish, Ictalurus punctatus. Branchial CA activity was highest in the cytoplasmic fraction, but activity was very low in mitochondria and microsomes. Erythrocyte CA activity was over four-fold greater than that in the gills. Intact animals were injected with the CA inhibitors acetazolamide and benzolamide. Slow, intra-arterial injection of both inhibitors elicited transient side effects of apnoea, bradycardia and hypoxaemia. Acetazolamide and benzolamide induced a mixed but primarily respiratory acidosis. The onset and the time course of the acidosis were correlated with the inhibition of erythrocyte CA; acetazolamide acted faster because it is more freely diffusible than benzolamide. The acid-base disturbance in the blood reached its maximum after 2 h; compensation was delayed until 24 h, when CA inhibition began to disappear. We conclude from these results that there is very little, if any, membrane-associated CA in the gill, and that the branchial enzyme is not quantitatively important in directly converting plasma HCO3- to CO2 for excretion. Rather, CO2 excretion is accomplished via the traditional chloride shift, followed by intracellular dehydration of HCO3- by erythrocyte CA. These results also suggest that branchial cytoplasmic CA inhibition might impair ion transport processes that are used to compensate blood acid-base disturbances and thus delay compensation of the respiratory acidosis.

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Arterial Po2, acid-base status, and red cell nucleoside triphosphates in rainbow trout transferred from fresh water to 20% sea water

Journal of Fish Biology ◽

10.1111/j.1095-8649.1993.tb00366.x ◽

1993 ◽

Vol 42 (4) ◽

pp. 611-614 ◽

Cited By ~ 3

Author(s):

B. K. Larsen ◽

F. B. Jensen

Keyword(s):

Rainbow Trout ◽

Fresh Water ◽

Sea Water ◽

Red Cell ◽

Acid Base ◽

Nucleoside Triphosphates ◽

Acid Base Status ◽

Arterial Po2

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Exercise and forced submergence in the pond slider (Trachemys scripta) and softshell turtle (Apalone ferox): influence on bimodal gas exchange, diving behaviour and blood acid-base status

Journal of Experimental Biology ◽

10.1242/jeb.202.3.267 ◽

1999 ◽

Vol 202 (3) ◽

pp. 267-278 ◽

Cited By ~ 3

Author(s):

B. Bagatto ◽

R.P. Henry

Keyword(s):

Gas Exchange ◽

Metabolic Stress ◽

Respiratory Acidosis ◽

Diving Behaviour ◽

Trachemys Scripta ◽

Acid Base ◽

Aerial Respiration ◽

Acid Base Status ◽

Softshell Turtle ◽

Apalone Ferox

The dynamics of bimodal respiration, diving behaviour and blood acid-base status in the softshell turtle Trachemys scripta and the pond slider Apalone ferox were investigated at rest and under conditions of stress induced by exercise and forced submergence. During periods of forced submergence, only A. ferox doubled its aquatic gas exchange rate. Both A. ferox and T. scripta increased their aerial gas exchange profoundly following exercise and forced submergence, a pattern indicative of increased anaerobic respiration. Emersion duration increased significantly in A. ferox following forced submergence, and mean apnoeic time decreased significantly in A. ferox following exercise, indicating that a larger proportion of time at the surface was spent ventilating. Also, A. ferox maintained a one-breath breathing bout regardless of treatment. Submergence produced a respiratory acidosis in the plasma of approximately 0.2 pH units in magnitude in T. scripta and a mixed respiratory/metabolic acidosis of 0.4 pH units in A. ferox. Exercise induced an acidosis of 0.2 pH units of primarily metabolic origin in both species. Intra-erythrocyte pH was also reduced in both species in response to submergence and exercise. Both intracellular and extracellular acidoses were more severe and longer lasting in A. ferox after each treatment. Plasma [HCO3-] decreased by 25 % in both species following exercise, but only in A. ferox following submergence. Plasma lactate concentrations increased by equal amounts in each species following exercise; however, they returned to resting concentrations sooner in T. scripta than in A. ferox. A. ferox had significantly higher lactate levels than T. scripta following forced submergence as well as a slower recovery time. A. ferox, which is normally a good bimodal gas exchanger at rest, utilizes aerial respiration to a greater extent when under respiratory and/or metabolic stress. T. scripta, although almost entirely dependent on aerial respiration, is physiologically better able to deal with the respiratory and metabolic stresses associated with both forced submergence and exercise.

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Effect of acetazolamide on gas exchange and acid-base control after maximal exercise

Journal of Applied Physiology ◽

10.1152/jappl.1992.72.1.278 ◽

1992 ◽

Vol 72 (1) ◽

pp. 278-287 ◽

Cited By ~ 29

Author(s):

J. M. Kowalchuk ◽

G. J. Heigenhauser ◽

J. R. Sutton ◽

N. L. Jones

Keyword(s):

Carbonic Anhydrase ◽

Muscle Power ◽

Inorganic Ions ◽

Carbonic Anhydrase Activity ◽

Co2 Production ◽

Acid Base ◽

Carbonic Anhydrase Inhibition ◽

Severe Exercise ◽

Arterial Plasma ◽

End Tidal

To investigate the interactions between the systems that contribute to acid-base homeostasis after severe exercise, we studied the effects of carbonic anhydrase inhibition on exchange of strong ions and CO2 in six subjects after 30 s of maximal isokinetic cycling exercise. Each subject exercised on two randomly assigned occasions, a control (CON) condition and 30 min after intravenous injection of 1,000 mg acetazolamide (ACZ) to inhibit blood carbonic anhydrase activity. Leg muscle power output was similar in the two conditions; peak O2 uptake (VO2) after exercise was lower in ACZ (2,119 +/- 274 ml/min) than in CON (2,687 +/- 113, P less than 0.05); peak CO2 production (VCO2) was also lower (2,197 +/- 241 in ACZ vs. 3,237 +/- 87 in CON, P less than 0.05) and was accompanied by an increase in the recovery half-time from 1.7 min in CON to 2.3 min in ACZ. Whereas end-tidal PCO2 was lower in ACZ than in CON, arterial PCO2 (PaCO2) was higher, and a large negative end-tidal-to-arterial difference (less than or equal to 20 Torr) was present in ACZ on recovery. In ACZ, postexercise increases in arterial plasma [Na+] and [K+] were greater but [La-] was lower. Arteriovenous differences across the forearm showed a greater uptake of La- and Cl- in CON than in ACZ. Carbonic anhydrase inhibition with ACZ, in addition to impairing equilibration of the CO2 system to the acid-base challenge of exercise, was accompanied by changes in equilibration of strong inorganic ions. A lowered plasma [La-] was not accompanied by greater uptake of La- by inactive muscle.

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Anesthetic effects on liver and muscle glycogen concentrations: rest and postexercise

Journal of Applied Physiology ◽

10.1152/jappl.1989.66.6.2895 ◽

1989 ◽

Vol 66 (6) ◽

pp. 2895-2900 ◽

Cited By ~ 8

Author(s):

T. I. Musch ◽

B. S. Warfel ◽

R. L. Moore ◽

D. R. Larach

Keyword(s):

Skeletal Muscles ◽

Respiratory Acidosis ◽

Blood Gases ◽

Arterial Blood Gases ◽

Acid Base ◽

Arterial Lactate ◽

Arterial Pco2 ◽

Arterial Blood ◽

Acid Base Status ◽

Gastrocnemius Muscles

We compared the effects of three different anesthetics (halothane, ketamine-xylazine, and diethyl ether) on arterial blood gases, acid-base status, and tissue glycogen concentrations in rats subjected to 20 min of rest or treadmill exercise (10% grade, 28 m/min). Results demonstrated that exercise produced significant increases in arterial lactate concentrations along with reductions in arterial Pco2 (PaCO2) and bicarbonate concentrations in all rats compared with resting values. Furthermore, exercise produced significant reductions in the glycogen concentrations in the liver and soleus and plantaris muscles, whereas the glycogen concentrations found in the diaphragm and white gastrocnemius muscles were similar to those found at rest. Rats that received halothane and ketamine-xylazine anesthesia demonstrated an increase in Paco2 and a respiratory acidosis compared with rats that received either anesthesia. These differences in arterial blood gases and acid-base status did not appear to have any effect on tissue glycogen concentrations, because the glycogen contents found in liver and different skeletal muscles were similar to one another cross all three anesthetic groups. These data suggest that even though halothane and ketamine-xylazine anesthesia will produce a significant amount of ventilatory depression in the rat, both anesthetics may be used in studies where changes in tissue glycogen concentrations are being measured and where adequate general anesthesia is required.

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Carbonic anhydrase 2 deficiency leads to increased pyelonephritis susceptibility

AJP Renal Physiology ◽

10.1152/ajprenal.00344.2014 ◽

2014 ◽

Vol 307 (7) ◽

pp. F869-F880 ◽

Cited By ~ 13

Author(s):

David S. Hains ◽

Xi Chen ◽

Vijay Saxena ◽

Evan Barr-Beare ◽

Weisi Flemming ◽

...

Keyword(s):

Carbonic Anhydrase ◽

Intercalated Cells ◽

Bacterial Clearance ◽

Wild Type ◽

Acid Base ◽

Wild Type Littermate ◽

Innate Defense ◽

Bacterial Response ◽

Infection Susceptibility ◽

Acid Base Status

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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