Relation of Na+ reabsorption to utilization of O2 and lactate in the perfused rat kidney

When the ratio delta TNa+/delta QO2 is used to estimate the energy requirements for net Na+ reabsorption (TNa+), it is assumed that the entire change in renal O2 uptake (delta QO2) is utilized only for the delta TNa+. However, if increases in renal synthetic work also occur when TNa+ is increased, the energy cost for TNa+ will be overestimated. We perfused the substrate-limited isolated rat kidney at 38 degrees C, pH 7.4, a mean arterial pressure of 120 mmHg, and mean lactate concentrations between 0 and 8.3 mM. We measured QO2, TNa+, net reabsorption of lactate (Tlac), net utilization of lactate (Qlac), lactate decarboxylation rate (Qlacox), as well as the net entry rate of lactate into biosynthetic pathways (Qxslac). When no exogenous substrate was present (rates are means, g wet wt-1 . min-1) GFR was 351 +/- 38 microliter, %TNa+ was 54 +/- 2%, and QO2 was 2.85 +/- 0.31 mumol; there was also a loss of about 20% of renal tissue K+ content. When mean [lactate] greater than or equal to 0.73 mM, the loss of tissue K+ was completely prevented and %TNa+ increased to and remained at about 85%. At mean [lactate] of 8.3 mM, Tlac was 5.1 +/- 0.6 mumol, QO2 was 6.12 +/- 1.24 mumol, and GFR was 709 +/- 83 microliter. Qlac, delta Qlacox and delta TNa+ increased in parallel with each other and approaches maximal rates as [lactate] was raised. By contrast, Tlac increased as a linear function of perfusate [lactate] and was not related to changes in Qlac. The molar increases in TNa+ were 10- to 20-fold greater than the increases in Tlac. It is more probable, therefore, that lactate enhances TNa+ by providing energy from its oxidation rather than by a co-transport phenomenon. At all concentrations of lactate, more lactate was utilized (Km = 1.2 mM; Vmax = 3.4) than was decarboxylated (Km = 1.6 mM; Vmax = 1.7), indicating that as lactate concentration increased, both the synthesis of new products from lactate and Na+ reabsorption increased. We conclude that the ratio delta TNa+/delta QO2, overestimates the energy cost of Na+ reabsorption. In order to obtain an accurate estimate of the energy requirements for TNa+ in kidney, the simultaneous changes in the rate of net biosynthetic work must also be quantified as TNa+ is changed.