Ramipril-induced decrease in renal lithium excretion in the rat.
1. The interaction of ramipril, an inhibitor of angiotensin I converting enzyme, with renal lithium handling 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 ramipril (1 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 intraperitonealy) was given as a single dose on the fifth day and renal functions were measured. 3. Ramipril induced a decrease in renal lithium clearance which was correlated with the decrease in the quantity of filtered lithium and the increase in the tubular fractional reabsorption of the metal. Ramipril also reduced the systolic blood pressure of the rats by about 15 mmHg. 4. In the absence of any effect on creatinine clearance or systolic blood pressure, indomethacin increased renal fractional lithium reabsorption and led to an increase in plasma lithium levels, as previously reported by our group. 5. In conclusions, our results indicate that ramipril decreases renal lithium excretion in Wistar rats, when given orally at a dose of 1 mg kg-1 day-1 over five days.
Barthelmebs
M
M
Institut de Pharmacologie (CNRS), Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
Grima
M
M
Imbs
J L
JL
D000803:Angiotensin I / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood / Q000652:urine; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008094:Lithium / Q000652:urine*; D019808:Losartan; D008297:Male; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000803:Angiotensin I; D008094:Lithium; D003404:Creatinine; D019808:Losartan; D017257:Ramipril; D007213:Indomethacin