Proximal tubular HCO 3 − , H+ and fluid transport during maleate-induced acidification defect

Abstract

The mechanism of tubular acidification was studied in proximal tubular acidification defect induced in rats by acute parenteral infusion of maleate (200 mg/kg), which causes diuresis and bicarbonaturia. Proximal tubular bicarbonate reabsorption and H+ ion secretion were determined by stopped-flow microperfusion and measurement of luminal pH by Sb microelectrodes. Stationary pH increased in proximal tubule from 6.78 to 7.25 and bicarbonate reabsorption decreased from 1.32 to 0.51 nmol/cm2 X s. In these segments, mean cell PD fell from -66.6 to -20.2 mV, while Jv as estimated by the Gertz technique fell to 15% of controls. A similar impairment of acidification was observed during luminal and capillary perfusion with phosphate Ringer's. Since H+-ion efflux from the lumen was not significantly increased and both acidification and alkalinization half-times (t/2) were increased, no evidence for an increase in passive permeability for H+/HCO3- was obtained. The increased t/2 found during luminal perfusion with acid phosphate indicates, according to an electrical analog model, a reduction in pump series conductance. These results show that maleate affects both proximal Na+ and H+ transport; this effect may be ascribed to impairment of sodium-dependent transport systems in the brush-border membrane.

Nuclear magnetic resonance‐ and mass spectrometry‐based metabolomics to study maleic acid toxicity from repeated dose exposure in rats

“…The aforementioned damages to the proximal renal tubules of the kidney, collectively known as Fanconi syndrome, can result in cell necrosis and renal tubular injury in the proximal tubules (Bunton, Fuller, Perry, & Shiner, ). With the mechanisms still unclear, animal studies demonstrated that MA inhibit the activity of Na‐K‐ATPase, H‐ATPase and Na/H antiporter on columnar cells; these interferences disrupt the transport of sodium ions, bicarbonates, as well as the pH balance of the kidney (Eiamong, Spohn, Kurtzman, & Sabatini, ; Everett et al, ; Reboucas, Fernandes, Elias, de Mello‐Aires, & Malnic, ).…”

“…transport of sodium ions, bicarbonates, as well as the pH balance of the kidney (Eiamong, Spohn, Kurtzman, & Sabatini, 1995;Everett et al, 1993;Reboucas, Fernandes, Elias, de Mello-Aires, & Malnic, 1984).…”

Combined in vivo and in vitro Approaches to Analysis of Renal Tubule Function

“…Using this method, it was possible to obtain evidence of a role of vacuolar H + -ATPase in the proximal tubule [32]; that in the proximal tubule adrenocortical hormones (aldosterone, corticosterone) support bicarbonate reabsorption [33]; that protein kinase C inhibits this transport, and that maleate causes a proximal tubule acidification defect [34]. More recently it was found that amphotericin B is responsible for a distal acidification defect which reduces the transepithelial pH gradient [31].…”