Altered expression of renal acid-base transporters in rats with lithium-induced NDI
Prolonged lithium treatment of humans and rodents often results in hyperchloremic metabolic acidosis. This is thought to be caused by diminished net H+ secretion and/or excessive back-diffusion of acid equivalents. To explore whether lithium treatment is associated with changes in the expression of key renal acid-base transporters, semiquantitative immunoblotting and immunocytochemistry were performed using kidneys from lithium-treated ( n = 6) and control ( n = 6) rats. Rats treated with lithium for 28 days showed decreased urine pH, whereas no significant differences in blood pH and plasma [Formula: see text] levels were observed. Immunoblot analysis revealed that lithium treatment induced a significant increase in the expression of the H+-ATPase (B1-subunit) in cortex (190 ± 18%) and inner stripe of the outer medulla (190 ± 9%), and a dramatic increase in inner medulla (900 ± 104%) in parallel to an increase in the expression of type 1 anion exchanger (400 ± 40%). This was confirmed by immunocytochemistry and immunoelectron microscopy, which also revealed increased density of intercalated cells. Moreover, immunoblotting and immunocytochemistry revealed a significant increase in the expression of the type 1 electrogenic [Formula: see text] cotransporter (NBC) in cortex (200 ± 23%) and of the electroneutral NBCn1 in inner stripe of the outer medulla (250 ± 54%). In contrast, there were no changes in the expression of Na+/H+ exchanger-3 or of the [Formula: see text] exchanger pendrin. These results demonstrate that the expression of specific renal acid-base transporters is markedly altered in response to long-term lithium treatment. This is likely to represent direct or compensatory effects to increase the capacity for [Formula: see text] reabsorption, [Formula: see text] reabsorption, and proton secretion to prevent the development of systemic metabolic acidosis.