Mechanisms of adaptation to chronic respiratory acidosis in the rabbit proximal tubule

Abstract

The hyperbicarbonatemia of chronic respiratory acidosis is maintained by enhanced bicarbonate reabsorption in the proximal tubule. To investigate the cellular mechanisms involved in this adaptation, cell and luminal pH were measured microfluorometrically using (2M,7')-bis(carboxyethyl)-(5,6)-carboxyfluorescein in isolated, microperfused S2 proximal convoluted tubules from control and acidotic rabbits. Chronic respiratory acidosis was induced by exposure to 10% CO2 for 52-56 h. Tubules from acidotic rabbits had a significantly lower luminal pH after 1-mm perfused length (7.03±0.09 vs. 7.26±0.06 in controls, perfusion rate = 10 nl/min). Chronic respiratory acidosis increased the initial rate of cell acidification (dpH1/dt) in response to luminal sodium removal by 63% and in response to lowering luminal pH (7.4-6.8) by 69%. Chronic respiratory acidosis also increased dpH,/dt in response to peritubular sodium removal by 63% and in response to lowering peritubular pH by 73%. In conclusion, chronic respiratory acidosis induces a parallel increase in the rates of the luminal Na/H antiporter and the basolateral Na/(HCO3)3 cotransporter. Therefore, the enhanced proximal tubule reabsorption of bicarbonate in chronic respiratory acidosis may be, at least in part, mediated by a parallel adaptation of these transporters.

Increased Na/H antiporter and Na/3HCO3 symporter activities in chronic hyperfiltration. A model of cell hypertrophy.

“…Arterial blood gases, plasma values, kidney weights, and transport rates are shown in Table II. There were no differences in arterial blood gases or plasma [Na], [K], or [CI], confirming that this protocol of chronic hyperfiltration was not associated with a systemic acid-base disorder or potassium deficiency, conditions previously shown to induce stimulatory adaptations in the apical membrane Na/H antiporter (Cohn et al, 1983;Kinsella et al, 1984;Seifter and Harris, 1984;Tsai et al, 1984;Harris et al, 1986;Jacobsen et al, 1986;Akiba et al, 1987;Talor et al, 1987;Preisig and Alpern, 1988;Krapf, 1989;Ruiz et al, 1989;Soleimani et al, 1990), basolateral membrane Na/3HCO~ symporter (Akiba et al, 1987;Preisig and Alpern, 1988;Krapf, 1989; 2 To calculate V/mm (cell volume per millimeter tubular length), the epithelial volume rather than cell water was used, and therefore cell volume has been overestimated to the extent that extraceUular and dry weight volumes contribute to epithelial volume. However, if we assume that the cell water increase in hypertrophy is proportional to the increase in epithelial volume, the results will be the same, although the absolute values may be slightly overestimated.…”

Distinct mechanisms underlie adaptation of proximal tubule Na+/H+ exchanger isoform 3 in response to chronic metabolic and respiratory acidosis

“…Promoter activity is given by the ratio of Nhe3 promoter signal (Firefly luciferase) by the transfection control (Renilla luciferase); *p<0.05 and, if the filtration rate is not affected, to a higher filtered bicarbonate load [27,38]. It has been shown that the metabolic compensation for respiratory acidosis is achieved by the kidneys [25,37], which increase the secretion of acid into the urine and the transport of HCO 3 − into the blood, thereby elevating plasma pH. Such compensation has been widely reported in patients with respiratory acidosis [2,16,26,47].…”

“…The relative amount of NHE3 normalised to actin was obtained by densitometric analysis using ImageJ software (Research Services Branch, National Institutes of Health, Bethesda, MD, USA). Various authors have demonstrated that hypercapnia activates NHE3 at the apical membrane of proximal tubule, albeit without an increase in the total amount of the exchanger [25,34].…”

“…Chronic respiratory acidosis in rats has also been associated with an increase in proximal tubule bicarbonate reabsorption [14]. Increased bicarbonate reabsorption in the proximal tubules of hypercapnic animals has been shown to be related to higher NHE activity in isolated tubules [25] and in renal microvillus vesicles [37]. Cultured renal proximal tubules exposed to high CO 2 tension (pCO 2 ) also present higher H + secretion [34].…”

Extracorporeal CO₂ Removal Integrated within a Continuous Renal Replacement Circuit Offers Multiple Advantages

“…In terms of acid-base equilibrium, the most commonly encountered perturbation in such patients is respiratory acidosis, which is commonly associated with a metabolic alkalosis [17]. Studies in rabbits have shown that chronic respiratory acidosis leads to an expression of the luminal Na/H antiporter and basolateral Na/HCO 3 cotransporter in proximal tubule cells [18]. This phenomenon is also accompanied by hypochloremia, which is explained by the existence of a Cl/HCO 3 exchanger called pendrin (SLC26A4, PDS) at the level of the apical domain of type B and non-A-non-B intercalated cells.…”