Early renal changes in lithium-treated normal and vasopressin-deficient rats

The effects of lithium (Li) on the kidney were studied in normal Long Evans (LE) rats and in rats of the Brattleboro strain (DI rats) which have a congenital (hypothalamic) diabetes insipidus. The rats received a moderate daily oral dose of Li for 4 weeks. The renal cortex of untreated DI rats showed no changes compared with LE rats, but in their medullary collecting ducts (CD) the cells appeared more voluminous, and by light microscope morphometry (outer medulla) their volume fraction was increased. Furthermore, there was an increase in the enzyme histochemical activities of succinate and alpha-glycerophosphate dehydrogenases, most pronounced in the inner medullary zone. Li-treated LE rats and DI rats both showed the same degree of cortical and medullary changes. In the cortex, the light microscope and enzyme histochemical changes were confined to the connecting tubules (CNT) and CD. In the outer and inner medullary zones the increase in CD volume fraction and enzyme activity was much more pronounced than in untreated DI rats. Morphometry of the inner stripe of the outer medullary zone showed the same decrease in the volume fraction of the distal straight tubules (DST) in DI rats with and without Li treatment, as well as in Li-treated LE rats compared with normal LE rats. This decrease may be due to the lack of vasopressin-mediated cyclic AMP generation in the DST of these three groups of animals. It is concluded that the changes induced by Li in the DST are likely to be due to impairment of the vasopressin response known to be present in this segment. However, in the CNT and in the cortical and medullary CD there are changes which are effects of Li not related to the cellular actions of vasopressin.