ABSENCE OF A LOSARTAN INTERACTION WITH RENAL LITHIUM EXCRETION IN THERAT

1 The interaction of losartan, a non-peptide specific ATI receptor ant agonist with the renal handling of lithium was analysed in conscious n ormotensive Wistar rats and compared with the known increase in renal tubular lithium reabsorption induced by the non-steroidal anti-inflamm atory drug, indomethacin. 2 The rats were treated for five days with l osartan (10 mgkg(-1) day(-1), orally), indomethacin (2.5 mg kg(-1) day (-1), intramuscularly) or their solvents. Lithium chloride (16.7 mg kg (-1), i.p.) was given as a single dose on the fifth day; renal functio ns were then measured. 3 Indomethacin, in the absence of any effect on creatinine clearance, increased renal fractional lithium reabsorption and led to an increase in plasma lithium levels. 4 Losartan did not m odify renal lithium handling and its plasma level. No change was obser ved in renal lithium clearance, the quantity of filtered lithium or th e fractional reabsorption of the metal. As expected, losartan had no e ffect on systolic blood pressure in normotensive rats. 5 In conclusion , our results indicate that losartan, when given orally is the rat at a dose of 10 mg kg(-1) day(-1) over five days, does not modify renal l ithium handling. They suggest that blockade of the angiotensin II rece ptors does not interfere with renal lithium reabsorption, which occurs mainly at a proximal tubular site.