Renal effects of lithium administration in rats: alterations in water and electrolyte metabolism and the response to vasopressin and cyclic-adenosine monophosphate during prolonged administration

Manuel Martinez-Maldonado, Amalia Stavroulaki-Tsapara, Nicolaos Tsaparas, Wadi N. Suki, Garabed Eknoyan

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Lithium (Li+) chloride, 2 to 3 mEq. per kilogram of body weight, was administered intraperitoneally to normal Wistar rats daily for 4 to 66 days. This resulted in a marked reduction in urine osmolality (Uosm.) and increase in the excretion of water, Na+, K+, uric acid, and phosphate. The excretion of uric acid and potassium was a direct function of UNaV. The magnitude of depression in urine osmolality was significantly related to the rate of excretion of lithium in the urine, suggesting that the change in water reabsorption is dependent on the presence of the ion in the luminal side of the tubule. During 2 per cent saline diuresis, Li+-treated rats achieved less fractional free water reabsorption ( TcH2O GFR × 100) at any level of fractional osmolar clearance ( Cosm. GFR × 100) than normal rats. On the other hand, during 0.225 per cent saline diuresis, fractional free water clearance ( CH2O GFR × 100) was normal over a wide range of fractional urine flow ( V GFR × 100), indicating intact function of the ascending limb of the loop of Henle. The intravenous infusion of vasopressin (VP) or dibutyryl cyclic-adenosine monophosphate (dcAMP) to Li+-treated rats resulted in a modest rise in Uosm. and a reduction in V GFR × 100 and CH2O GFR × 100. Although the response to VP appeared earlier than that to dibutyryl cyclic-AMP, the magnitude of the changes in Uosm., V GFR × 100, and CH2O GFR × 100 was eventually the same with both substances. Comparison between normal and Li+-treated rats revealed that the response to both VP and dibutyryl cyclic-AMP was blunted, albeit to a greater extent in the former. Inhibition by Li+ of adenylate cyclase will only partially explain the present data. Impairment in the release of endogenous VP or a block distal to the formation of cyclic-AMP must have played a role. In view of a normal diluting capacity and the increase in the excretion of phosphate and uric acid, it is suggested that Li+, when administered chronically in the present doses, inhibits proximal tubular reabsorption.

Original languageEnglish (US)
Pages (from-to)445-461
Number of pages17
JournalThe Journal of Laboratory and Clinical Medicine
Volume86
Issue number3
StatePublished - Jan 1 1975

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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