Absence of a losartan interaction with renal lithium excretion in the rat.
1. The interaction of losartan, a non-peptide specific AT1 receptor antagonist with the renal handling of lithium was analysed in conscious normotensive Wistar rats and compared with the known increase in renal tubular lithium reabsorption induced by the non-steroidal anti-inflammatory drug, indomethacin. 2. The rats were treated for five days with losartan (10 mg kg-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 functions 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 modify renal lithium handling and its plasma level. No change was observed in renal lithium clearance, the quantity of filtered lithium or the fractional reabsorption of the metal. As expected, losartan had no effect on systolic blood pressure in normotensive rats. 5. In conclusion, our results indicate that losartan, when given orally in the rat at a dose of 10 mg kg-1 day-1 over five days, does not modify renal lithium handling. They suggest that blockade of the angiotensin II receptors does not interfere with renal lithium reabsorption, which occurs mainly at a proximal tubular site.
Barthelmebs
M
M
Institut de Pharmacologie (ERS 109/CNRS), Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
Alt-Tebacher
M
M
Madonna
O
O
Grima
M
M
Imbs
J L
JL
D000803:Angiotensin I / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008094:Lithium / Q000652:urine*; D019808:Losartan; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology*; D014563:Urodynamics / Q000187:drug effects; D014882:Water-Electrolyte Balance / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000803:Angiotensin I; D008094:Lithium; D003404:Creatinine; D019808:Losartan; D007213:Indomethacin