Effects of inorganic lead in vitro on ion exchanges and respiratory metabolism of rat kidney cortex

Abstract
The effects of Pb2+ added in vitro to tissue slices, isolated tubules and isolated mitochondria of rat kidney cortex have been studied. Slices were depleted of K+ and loaded with Na+, Cl and water by pre-incubation at 1° C, and reversal of these changes was then induced by incubation under metabolically favourable conditions. The net reaccumulation of K+ was reduced by a maximum of 30% when Pb2+ was present in the medium, the maximal effect being caused by 200 μM Pb2+. Lead also caused a reduction of Na+ extrusion which was approximately equimolar with its effect on K+, but it did not affect the extrusion of Cl and water. The initial rates of the net, active movements of K+ and Na+ were not altered by Pb2+, divergence from control values only being noted after 15–30 min incubation. The O2 consumption and the ATP content were 25–30% lower in slices incubated with 200 μM Pb+ than in control slices; the effect on ATP content was not observed until incubation had continued for 30 min. In tubules isolated from the renal cortex, the rate of respiration (50%) and ATP content (30%) were also partly reduced by 200 μM Pb2+. The consumption of O2 by mitochondria isolated from the cortex was much more sensitive to Pb2+ added in vitro than the respiration of intact cells; the rate of respiration in state 3 (presence of phosphate acceptor) and the respiratory control ratio were drastically reduced, with half-maximal inhibition at 30 and 20 μM Pb2+ respectively. Comparison of the effects of Pb2+ on energy metabolism and ion transport of the slices with the corresponding effects of antimycin A and ouabain suggests that Pb2+ inhibited K+ and Na+ transport mainly as a consequence of a primary inhibition of the provision of ATP.