Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1995 Oct;116(4):2166–2169. doi: 10.1111/j.1476-5381.1995.tb15049.x

Absence of a losartan interaction with renal lithium excretion in the rat.

M Barthelmebs 1, M Alt-Tebacher 1, O Madonna 1, M Grima 1, J L Imbs 1
PMCID: PMC1908966  PMID: 8564244

Abstract

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.

Full text

PDF
2166

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Atherton J. C., Green R., Higgins A., Large A., McNicholas C., Parker D., Pempkowiak L., Rajani K., Smith J. Lithium clearance in healthy humans: effects of sodium intake and diuretics. Kidney Int Suppl. 1990 Mar;28:S36–S38. [PubMed] [Google Scholar]
  2. Barthelmebs M., Grima M., Imbs J. L. Ramipril-induced decrease in renal lithium excretion in the rat. Br J Pharmacol. 1995 Oct;116(4):2161–2165. doi: 10.1111/j.1476-5381.1995.tb15048.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bunkenburg B., Schnell C., Baum H. P., Cumin F., Wood J. M. Prolonged angiotensin II antagonism in spontaneously hypertensive rats. Hemodynamic and biochemical consequences. Hypertension. 1991 Sep;18(3):278–288. doi: 10.1161/01.hyp.18.3.278. [DOI] [PubMed] [Google Scholar]
  4. Cogan M. G., Liu F. Y., Wong P. C., Timmermans P. B. Comparison of inhibitory potency by nonpeptide angiotensin II receptor antagonists PD123177 and DuP 753 on proximal nephron and renal transport. J Pharmacol Exp Ther. 1991 Nov;259(2):687–691. [PubMed] [Google Scholar]
  5. Douste-Blazy P., Rostin M., Livarek B., Tordjman E., Montastruc J. L., Galinier F. Angiotensin converting enzyme inhibitors and lithium treatment. Lancet. 1986 Jun 21;1(8495):1448–1448. doi: 10.1016/s0140-6736(86)91598-9. [DOI] [PubMed] [Google Scholar]
  6. Greger R. Possible sites of lithium transport in the nephron. Kidney Int Suppl. 1990 Mar;28:S26–S30. [PubMed] [Google Scholar]
  7. Griffin J. H., Hahn S. M. Lisinopril-induced lithium toxicity. DICP. 1991 Jan;25(1):101–101. doi: 10.1177/106002809102500123. [DOI] [PubMed] [Google Scholar]
  8. Imbs J. L., Singer L., Danion J. M., Schmidt M., Zawilslak R. Effects of indomethacin and methylprednisolone on renal elimination of lithium in the rat. Int Pharmacopsychiatry. 1980;15(3):143–149. doi: 10.1159/000468430. [DOI] [PubMed] [Google Scholar]
  9. Knox F. G., Schneider E. G., Willis L. R., Strandhoy J. W., Ott C. E. Editorial: Site and control of phosphate reabsorption by the kidney. Kidney Int. 1973 Jun;3(6):347–353. doi: 10.1038/ki.1973.56. [DOI] [PubMed] [Google Scholar]
  10. Koomans H. A., Dorhout Mees E. J. Lithium in renal physiology: post-conference discussion and consensus. Kidney Int Suppl. 1990 Mar;28:S78–S79. [PubMed] [Google Scholar]
  11. Leyssac P. P. Validity of the lithium clearance concept assessed with micropuncture studies. Kidney Int Suppl. 1990 Mar;28:S17–S21. [PubMed] [Google Scholar]
  12. Reimann I. W., Diener U., Frölich J. C. Indomethacin but not aspirin increases plasma lithium ion levels. Arch Gen Psychiatry. 1983 Mar;40(3):283–286. doi: 10.1001/archpsyc.1983.01790030053006. [DOI] [PubMed] [Google Scholar]
  13. Thomsen K. Lithium clearance as a measure of sodium and water delivery from the proximal tubules. Kidney Int Suppl. 1990 Mar;28:S10–S16. [PubMed] [Google Scholar]
  14. Vanhoutte P. M., Boulanger C. M., Illiano S. C., Nagao T., Vidal M., Mombouli J. V. Endothelium-dependent effects of converting-enzyme inhibitors. J Cardiovasc Pharmacol. 1993;22 (Suppl 5):S10–S16. doi: 10.1097/00005344-199322005-00003. [DOI] [PubMed] [Google Scholar]
  15. Wong P. C., Price W. A., Chiu A. T., Duncia J. V., Carini D. J., Wexler R. R., Johnson A. L., Timmermans P. B. Nonpeptide angiotensin II receptor antagonists. VIII. Characterization of functional antagonism displayed by DuP 753, an orally active antihypertensive agent. J Pharmacol Exp Ther. 1990 Feb;252(2):719–725. [PubMed] [Google Scholar]
  16. Wong P. C., Price W. A., Jr, Chiu A. T., Duncia J. V., Carini D. J., Wexler R. R., Johnson A. L., Timmermans P. B. In vivo pharmacology of DuP 753. Am J Hypertens. 1991 Apr;4(4 Pt 2):288S–298S. doi: 10.1093/ajh/4.4.288s. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES