Factors affecting proximal tubular acidification of non‐bicarbonate buffer in the rat.

Abstract

SUMMARY1. The effect of peritubular PCO2 and pH changes within the physiological range on proximal tubular acidification ofnon-bicarbonate (phosphate) buffer was evaluated with and without carbonic anhydrase inhibition by stopped-flow microperfusion and Sb micro-electrode techniques.2. Luminal steady-state pH was reduced from 6-69 to 6-37 and H ion fluxes (JH+)increased from 0-63 to 1-57 nmol cm-2 s-1 by increasing capillary CO2 from 0 to 9-6 % at pH 7-2. 3. After acetazolamide a marked, although attenuated, effect ofCO2 on acidification was still observed; JH+ increased from 0-088 nmol cm-2 s-1 at 0 % CO2 to 0-78 at 9-6% CO2. Most of this effect can be explained by titration of luminal buffer by C02, uncatalysed CO2 hydration and H2CO3 recirculation.4. An increase in capillary CO2 reduced acidification half-times (t/2), which, according to an analogue circuit model, may be due to increased H ion access to the pump.5. Peritubular pH changes at 0 % CO2 also modified tubular acidification, increasing JH+ from 0-73 nmol cm-2 s-1 at pH 7-6 to 0 99 at pH 7 0. After acetazolamide, JH+ still increased from 0.11 nmol cm-2 s-1 at pH 7-6 to 0 57 at pH 7 0. 6. In conclusion, both peritubular C02 changes at constant pH and pH changes at 0 % C02 were effective to modify JH+, in the presence and absence of carbonic anhydrase activity. In the studied range, capillary C02 induced larger changes in JH+ than pH. The data show substrate (H ion) is a limiting factor for tubular H ion secretion.

Relative contribution of V‐H+ATPase and NA+/H+ exchanger to bicarbonate reabsorption in proximal convoluted tubules of old rats

“…Therefore, bicarbonate concentration falls and reaches steady state. Detailed treatments of this model have been previously published (Amorena et al, 1984). Using pH values recorded from microelectrode measurements, concentration at time t is calculated according to:…”

Regulation of nephron acidification by corticosteroids

“…This stimulation is thought to occur by membrane insertion or activation of transporters, which is compatible with our findings in the proximal tubule. In these experiments there was only a relatively small effect on the transepithelial pH gradient, which depends on the sodium gradient across the apical cell membrane, and a large modification of the acidification half-time, which, according to a model of proximal tubule cells, depends on the number or turnover of transport sites within the membrane (34). In proximal tubules, not all H + -ion secretion is due to Na + /H + exchange, but some 20-30% have been shown to depend on vacuolar H + -ATPase, which of course could also undergo the action of these hormones (26).…”

Dinitrophenol effect on proximal tubular acidification in the rat.

“…A consequence common to both acidification and alkalinization curves is the progressive increase in steady-state pH levels, indicating a progressively decreasing ability of the tubular epithelial cell to maintain a pH gradient. Amorena et al (1984) described an electrical analog model for H-ion secretion in the renal tubule that is able to explain the kinetic characteristics of renal tubular acidification. This model consists of three elements: (1) a H-ion pump (E) associated with its series resistance (Ri); (2) a shunt path (Rj) which could be trans or paracellular; and (3) a capacitance (C) which is related to the buffering capacity of the tubular lumen.…”

“…The methods of anaesthesia, animal preparation and micropuncture have been described previously (De Mello Aires & Malnic, 1975;Amorena et al 1984). The rats received an intravenous infusion of 3 % mannitol in normal saline at the rate of0-05 ml/min during the experiment.…”

“…The final transepithelial H-ion gradient depends not only on the magnitude of the H-ion transport rate, but also on the back-leak of H ion from lumen to interstitium and on the leak of bicarbonate from the interstitium to the lumen via the paracellular pathway (Amorena, Fernandes & Malnic, 1984; Chan, Malnic & Giebisch, 1983). Changes in the permeability of the tubule to H ion are, therefore, expected to affect urinary acidification.…”