Deficiency of carbonic anhydrase in the vasculature of rabbit kidneys.

Effros, Richard M.; Nioka, Shoko

doi:10.1172/jci110895

Cited by 11 publications

(5 citation statements)

References 40 publications

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“…Regional changes in blood flow during graded CA inhibition are ignored. We have assumed that CA activity is present on the endothelium of all tissue capillaries, which is not likely to be true (14).…”

Section: Discussionmentioning

confidence: 99%

Kinetics of CO₂excretion and intravascular pH disequilibria during carbonic anhydrase inhibition

Cárdenas

Heming

Bidani

1998

Journal of Applied Physiology

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Inhibition of carbonic anhydrase (CA) activity (activity in red blood cells and activity available on capillary endothelium) results in decrements in CO2 excretion (VCO2) and plasma-erythrocyte CO2-HCO(-3)-H+ disequilibrium as blood travels around the circulation. To investigate the kinetics of changes in blood PCO2 and pH during progressive CA inhibition, we used our previously detailed mathematical model of capillary gas exchange to analyze experimental data of VCO2 and blood-gas/pH parameters obtained from anesthetized, paralyzed, and mechanically ventilated dogs after treatment with acetazolamide (Actz, 0-100 mg/kg i.v.). Arterial and mixed venous blood samples were collected via indwelling femoral and pulmonary arterial catheters, respectively. Cardiac output was measured by thermodilution. End-tidal PCO2, as a measure of alveolar PCO2, was obtained from continuous records of airway PCO2 above the carina. Experimental results were analyzed with the aid of a mathematical model of lung and tissue-gas exchange. Progressive CA inhibition was associated with stepwise increments in the equilibrated mixed venous-alveolar PCO2 gradient (9, 19, and 26 Torr at 5, 20, and 100 mg/kg Actz, respectively). The maximum decrements in VCO2 were 10, 24, and 26% with 5, 20, and 100 mg/kg Actz, respectively, without full recovery of VCO2 at 1 h postinfusion. Equilibrated arterial PCO2 overestimated alveolar PCO2, and tissue PCO2 was underestimated by the measured equilibrated mixed venous blood PCO2. Mathematical model computations predicted hysteresis loops of the instantaneous CO2-HCO(-3)-H+ relationship and in vivo blood PCO2-pH relationship due to the finite reaction times for CO2-HCO(-3)-H+ reactions. The shape of the hysteresis loops was affected by the extent of Actz inhibition of CA in red blood cells and plasma.

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Section: Discussionmentioning

confidence: 99%

Kinetics of CO₂excretion and intravascular pH disequilibria during carbonic anhydrase inhibition

Cárdenas

Heming

Bidani

1998

Journal of Applied Physiology

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“…the possibility of an effect on this enzyme within the renal vessels, which in turn might alter the local acid-base composition and trig ger an increase in vascular resistance, should be entertained. However, endothelial cells from the renal vasculature, particularly those from glomerular capillaries, and all larger ves sels are distinctly deficient in CA [24,25]. A direct effect of acetazolamide on macula densa/juxtaglomerular apparatus might also oc cur as a result of local changes in tissue acidity mediated by CA inhibition [26].…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Acetazolamide-Induced Rise in Renal Vascular Resistance Assessed in the Dog Whole Kidney

Yeyati

Altenberg²,

Adrogué³

1992

Kidney Blood Press Res

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The reduction in renal blood flow (RBF) and glomerular filtration rate (GFR) observed after the administration of the carbonic anhydrase inhibitors acetazolamide and benzolamide had been explained as due to activation of the tubuloglomerular feedback mechanism. If correct, pharmacologic blockade of this pathway should prevent the development of renal vasoconstriction with the carbonic anhydrase inhibitors. Thus, the current study evaluates in the dog whole kidney the effect of acetazolamide (20 mg/ kg body weight) in the presence or absence of furosemide (5 mg/kg body weight), a drug which blocks the tubuloglomerular feedback. Acetazolamide resulted in a large increase in urinary bicarbonate excretion accompanied by a significant reduction in GFR (16%) and RBF (18%). By contrast with the effects of acetazolamide, furosemide did not alter GFR and increased RBF. In addition, the loop diuretic induced a large chloruresis without changes in urinary bicarbonate excretion. The infusion of acetazolamide in furosemide-treated dogs resulted in a significant increment in renal bicarbonate excretion and in a significant reduction in the levels of both GFR (28%) and RBF (13%). Therefore, furosemide pretreatment did not block the effects of acetazolamide on renal hemodynamic parameters. Consequently, the acetazolamide-induced reduction in both GFR and RBF cannot ba accounted for by changes in chloride levels in the juxtaglomerular region due to enhanced salt transport in the macula densa/distal nephron. The increased renal vascular resistance observed with acetazolamide might occur by either a direct effect of this agent on the renal circulation or as a result of changes in intrarenal pressure secondary to the inhibition of proximal fluid reabsorption.

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“…Moreover, a reduction in RBF is only one possible explanation for the higher Pco2 values. Recent work has implicated chemical disequilibrium between C02 and HCO3 in the renal vasculature and vascularvascular exchange of C02 as factors contributing to the high Pco2 in the renal cortex (16,17). Whether these factors contribute to the differences in cortical Pco2 between control and CMA rats remains a subject for future investigation.…”

Section: Discussionmentioning

confidence: 99%

“…The loops were confirmed as being the last accessible proximal convolutions by the failure of a small injected oil droplet to reappear in any subsequent proximal loop on the surface of the kidney. Timed collections (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) Pco2 measurements. The Pco2 microelectrodes used in these studies were constructed as described previously (8), and had outer tip diameters of [4][5][6][7][8][9][10] The ability of our microelectrode system to detect small differences in Pco2, with the recorder set at 1 mV = 5 mm, was tested by using it to measure Pco2 in three solutions equilibrated with known gas mixtures (Pco2 values of 30.9, 32.4, and 35.9 mmHg as determined by Scholander analysis).…”

Section: Methodsmentioning

confidence: 99%

Proximal tubular bicarbonate reabsorption and PCO2 in chronic metabolic alkalosis in the rat.

Maddox¹,

Gennari²

1983

J. Clin. Invest.

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A B S T R A C T Studies were undertaken to define the pattern of proximal tubular bicarbonate reabsorption and its relation to tubular and capillary Pco2 in rats with chronic metabolic alkalosis (CMA). CMA was induced by administering furosemide to rats ingesting a low electrolyte diet supplemented with NaHCO3 and KHC03. Proximal tubular bicarbonate reabsorption and Pco2 were measured in CMA rats either 4-7 or 11-14 d after furosemide injection, in order to study a wide range of filtered bicarbonate loads. A group of nine age-matched control animals, fed the same diet but not given furosemide, was studied for comparison. In a third group of controls, the filtered load of bicarbonate was varied over the same range as in the CMA rats by plasma infusion and aortic constriction. The CMA rats had significant alkalemia and hypokalemia (4-7 d: pH 7.58, HCO3 38.3 meq/liter, K+ 2.1 meq/liter; 11-14 d: pH 7.54, HCO3 38.1 meq/liter, K+ 2.5 meq/liter). Nonetheless, proximal bicarbonate reabsorption was not significantly different from that seen in control rats at any given load of filtered bicarbonate (from 250 to 1,300 pmol/min). In both control and CMA rats, 83-85% of the filtered bicarbonate was reabsorbed by the end of the accessible proximal tubule. These observations indicate that proximal bicarbonate reabsorption is determined primarily by the filtered load in chronic metabolic alkalosis. When single nephron glomerular filtration rate (SNGFR) is reduced by volume depletion in the early postfurosemide period, the filtered load and the rate of proximal bicarbonate reabsorption remain at or below control lev-

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Deficiency of carbonic anhydrase in the vasculature of rabbit kidneys.

Cited by 11 publications

References 40 publications

Kinetics of CO₂excretion and intravascular pH disequilibria during carbonic anhydrase inhibition

Kinetics of CO₂excretion and intravascular pH disequilibria during carbonic anhydrase inhibition

Mechanism of Acetazolamide-Induced Rise in Renal Vascular Resistance Assessed in the Dog Whole Kidney

Proximal tubular bicarbonate reabsorption and PCO2 in chronic metabolic alkalosis in the rat.

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Deficiency of carbonic anhydrase in the vasculature of rabbit kidneys.

Cited by 11 publications

References 40 publications

Kinetics of CO2excretion and intravascular pH disequilibria during carbonic anhydrase inhibition

Kinetics of CO2excretion and intravascular pH disequilibria during carbonic anhydrase inhibition

Mechanism of Acetazolamide-Induced Rise in Renal Vascular Resistance Assessed in the Dog Whole Kidney

Proximal tubular bicarbonate reabsorption and PCO2 in chronic metabolic alkalosis in the rat.

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Kinetics of CO₂excretion and intravascular pH disequilibria during carbonic anhydrase inhibition

Kinetics of CO₂excretion and intravascular pH disequilibria during carbonic anhydrase inhibition