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Chemical Compound Review

losartan     [2-butyl-5-chloro-3-[[4-[2- (2H-tetrazol-5...

Synonyms: Losartic, Cozaar, DuP-753, MK-954, DuP 753, ...
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Disease relevance of losartan


Psychiatry related information on losartan

  • RESULTS: A total of 327 patients in the losartan group reached the primary end point, as compared with 359 in the placebo group (risk reduction, 16 percent; P=0.02) [1].
  • CONCLUSIONS : Both the angiotensin converting enzyme inhibitor enalapril and the AT1 receptor blocking agent losartan acted similarly on pain threshold and tolerance, pain sensitivity being increased during the two anti-hypertensive treatments [6].
  • 3. When given after 6 h of water deprivation, losartan and EXP 3174 produced directionally similar, but temporally disparate, haemodynamic effects [7].
  • The potent and selective orally active ANG II receptor antagonist losartan (DuP 753) enhanced the retentions in an inhibitory (passive) avoidance test after scopolamine amnesia [8].
  • In summary, the results of this open-label, uncontrolled study suggest that chronic treatment with losartan may improve ventilatory efficiency and decrease plasma brain natriuretic peptide concentrations with the improvement of physical activity and left ventricular systolic function in patients with CHF [9].

High impact information on losartan


Chemical compound and disease context of losartan


Biological context of losartan


Anatomical context of losartan


Associations of losartan with other chemical compounds

  • Intrarenal administration of angiotensin II receptor type 1 (AT1) receptor antagonists losartan or EXP-3174 simultaneously with ANG II caused dose-dependent inhibition of ANG II responses [29].
  • Neither losartan nor PD123177 alone significantly inhibited ANG II-evoked NO release, and when cells were stimulated with ANG II in the presence of losartan (10 microM) and PD123177 (10 microM) in combination, NO release was significantly inhibited (P < 0.05) [30].
  • This inhibitory effect of AII on IRS-1/PI 3-kinase association was blocked by the AII receptor antagonist saralasin, but not by AT1 antagonist losartan or AT2 antagonist PD123319 [31].
  • METHODS: We randomly assigned 722 ACE inhibitor naive patients (aged 65 years or more) with New York Heart Association (NYHA) class II-IV heart failure and ejection fractions of 40% or less to double-blind losartan (n = 352) titrated to 50 mg once daily or captopril (n = 370) titrated to 50 mg three times daily, for 48 weeks [32].
  • The primary endpoint occurred in 103 patients assigned losartan (n=586) and 139 assigned atenolol (n=609); relative risk 0.76 (95% CI 0.58-.98), p=0.31 [33].

Gene context of losartan

  • Treatment with either losartan (25 mg x kg(-1) x d(-1)) or hydralazine (15 mg x kg(-1) x d(-1)), both of which prevented the Ang II-induced hypertension, blocked HO-1 mRNA upregulation [34].
  • Stably expressed in COS-7 cells, the receptor showed selective binding to AT2-specific ligands PD123319 and CGP42112A but not to the AT1-specific ligand, losartan [35].
  • On this basis we hypothesized that BLEO-induced apoptosis and lung fibrosis in mice would be inhibited by the AT1 antagonist losartan (LOS) or by targeted deletion of the AT1 gene [36].
  • Treatment of AT1 receptor-expressing VSMC with AngII resulted in a dose-dependent and time-dependent increase (2- to 4-fold) in (3)H-glucosamine/(35)S-sulfate incorporation, which was abolished by pretreatment with the AT1 receptor antagonist, losartan [37].
  • The AngII receptor (AT1) antagonist Losartan (10 microM) prevented AngII-induced, but not stretch-induced, VEGF protein secretion (AngII 1.7+/-0.3, AngII + Losartan 1.0+/-0.1, P<0.05; stretch 2.4+/-0.4, stretch + Losartan 2.6+/-0.5) [38].

Analytical, diagnostic and therapeutic context of losartan

  • METHODS: A total of 1513 patients were enrolled in this randomized, double-blind study comparing losartan (50 to 100 mg once daily) with placebo, both taken in addition to conventional antihypertensive treatment (calcium-channel antagonists, diuretics, alpha-blockers, beta-blockers, and centrally acting agents), for a mean of 3.4 years [1].
  • The composite of morbidity and mortality from cardiovascular causes was similar in the two groups, although the rate of first hospitalization for heart failure was significantly lower with losartan (risk reduction, 32 percent; P=0.005) [1].
  • This was completely abrogated by simultaneous losartan perfusion [39].
  • Losartan and renal transplantation [40].
  • To examine the importance of AT1 receptor expression, another group of isolated rat hearts (n=5) was perfused with buffer containing losartan (10(-5) mol/L) and subjected to ischemia followed by reperfusion [41].


  1. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. Brenner, B.M., Cooper, M.E., de Zeeuw, D., Keane, W.F., Mitch, W.E., Parving, H.H., Remuzzi, G., Snapinn, S.M., Zhang, Z., Shahinfar, S. N. Engl. J. Med. (2001) [Pubmed]
  2. Losartan-induced azotemia in a diabetic recipient of a kidney transplant. Cohen, L.S., Friedman, E.A. N. Engl. J. Med. (1996) [Pubmed]
  3. Effects of losartan on cardiovascular morbidity and mortality in patients with isolated systolic hypertension and left ventricular hypertrophy: a Losartan Intervention for Endpoint Reduction (LIFE) substudy. Kjeldsen, S.E., Dahlöf, B., Devereux, R.B., Julius, S., Aurup, P., Edelman, J., Beevers, G., de Faire, U., Fyhrquist, F., Ibsen, H., Kristianson, K., Lederballe-Pedersen, O., Lindholm, L.H., Nieminen, M.S., Omvik, P., Oparil, S., Snapinn, S., Wedel, H. JAMA (2002) [Pubmed]
  4. Losartan and severe migraine. Ahmad, S. JAMA (1995) [Pubmed]
  5. Angiotensin II stimulates proliferation of normal early erythroid progenitors. Mrug, M., Stopka, T., Julian, B.A., Prchal, J.F., Prchal, J.T. J. Clin. Invest. (1997) [Pubmed]
  6. Changes in pain perception during treatment with angiotensin converting enzyme-inhibitors and angiotensin II type 1 receptor blockade. Guasti, L., Zanotta, D., Diolisi, A., Garganico, D., Simoni, C., Gaudio, G., Grandi, A.M., Venco, A. J. Hypertens. (2002) [Pubmed]
  7. Comparison of the regional haemodynamic effects of the AT1-receptor antagonists, losartan and EXP 3174, in water-deprived Brattleboro rats. Widdop, R.E., Gardiner, S.M., Kemp, P.A., Bennett, T. Br. J. Pharmacol. (1993) [Pubmed]
  8. Involvement of nitric oxide-formation in the action of losartan (DuP 753): effects in an inhibitory avoidance model. Hock, F.J. Behav. Brain Res. (1994) [Pubmed]
  9. Effects of angiotensin II type 1 receptor antagonist, losartan, on ventilatory response to exercise and neurohormonal profiles in patients with chronic heart failure. Kinugawa, T., Kato, M., Ogino, K., Osaki, S., Igawa, O., Hisatome, I., Shigemasa, C. Jpn. J. Physiol. (2004) [Pubmed]
  10. Absence of angiotensin II type 1 receptor in bone marrow-derived cells is detrimental in the evolution of renal fibrosis. Nishida, M., Fujinaka, H., Matsusaka, T., Price, J., Kon, V., Fogo, A.B., Davidson, J.M., Linton, M.F., Fazio, S., Homma, T., Yoshida, H., Ichikawa, I. J. Clin. Invest. (2002) [Pubmed]
  11. Angiotensin II attenuates renal cortical cyclooxygenase-2 expression. Cheng, H.F., Wang, J.L., Zhang, M.Z., Miyazaki, Y., Ichikawa, I., McKanna, J.A., Harris, R.C. J. Clin. Invest. (1999) [Pubmed]
  12. Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases the Bcl-2-to-Bax protein ratio in the cell. Leri, A., Claudio, P.P., Li, Q., Wang, X., Reiss, K., Wang, S., Malhotra, A., Kajstura, J., Anversa, P. J. Clin. Invest. (1998) [Pubmed]
  13. Angiotensin AT1 receptor blockade abolishes the reflex sympatho-excitatory response to adenosine. Rongen, G.A., Brooks, S.C., Ando, S., Abramson, B.L., Floras, J.S. J. Clin. Invest. (1998) [Pubmed]
  14. Angiotensin II causes weight loss and decreases circulating insulin-like growth factor I in rats through a pressor-independent mechanism. Brink, M., Wellen, J., Delafontaine, P. J. Clin. Invest. (1996) [Pubmed]
  15. Effects of losartan and captopril on QT dispersion in elderly patients with heart failure. ELITE study group. Brooksby, P., Robinson, P.J., Segal, R., Klinger, G., Pitt, B., Cowley, A.J. Lancet (1999) [Pubmed]
  16. Randomized comparison of long-term losartan versus propranolol in lowering portal pressure in cirrhosis. González-Abraldes, J., Albillos, A., Bañares, R., Del Arbol, L.R., Moitinho, E., Rodríguez, C., González, M., Escorsell, A., García-Pagán, J.C., Bosch, J. Gastroenterology (2001) [Pubmed]
  17. Effects of enalapril versus losartan on regression of volume overload-induced cardiac hypertrophy in rats. Ruzicka, M., Yuan, B., Leenen, F.H. Circulation (1994) [Pubmed]
  18. The mechanism of improved sodium homeostasis of low-dose losartan in preascitic cirrhosis. Wong, F., Liu, P., Blendis, L. Hepatology (2002) [Pubmed]
  19. Expression of type II cGMP-dependent protein kinase in rat kidney is regulated by dehydration and correlated with renin gene expression. Gambaryan, S., Häusler, C., Markert, T., Pöhler, D., Jarchau, T., Walter, U., Haase, W., Kurtz, A., Lohmann, S.M. J. Clin. Invest. (1996) [Pubmed]
  20. Role of AT1 receptors in the resetting of the baroreflex control of heart rate by angiotensin II in the rabbit. Wong, J., Chou, L., Reid, I.A. J. Clin. Invest. (1993) [Pubmed]
  21. Failure of losartan to control blood pressure in scleroderma renal crisis. Caskey, F.J., Thacker, E.J., Johnston, P.A., Barnes, J.N. Lancet (1997) [Pubmed]
  22. Losartan and fetal toxic effects. Saji, H., Yamanaka, M., Hagiwara, A., Ijiri, R. Lancet (2001) [Pubmed]
  23. Losartan reduces hematocrit in patients with chronic obstructive pulmonary disease and secondary erythrocytosis. Vlahakos, D.V., Marathias, K.P., Kosmas, E.N. Ann. Intern. Med. (2001) [Pubmed]
  24. Hemodynamic and neurohormonal effects of the angiotensin II antagonist losartan in patients with congestive heart failure. Gottlieb, S.S., Dickstein, K., Fleck, E., Kostis, J., Levine, T.B., LeJemtel, T., DeKock, M. Circulation (1993) [Pubmed]
  25. Improved exercise tolerance after losartan and enalapril in heart failure: correlation with changes in skeletal muscle myosin heavy chain composition. Vescovo, G., Dalla Libera, L., Serafini, F., Leprotti, C., Facchin, L., Volterrani, M., Ceconi, C., Ambrosio, G.B. Circulation (1998) [Pubmed]
  26. Control of carotid vasomotor tone by local renin-angiotensin system in normotensive and spontaneously hypertensive rats. Role of endothelium and flow. Caputo, L., Tedgui, A., Lévy, B.I. Circ. Res. (1995) [Pubmed]
  27. Angiotensin II induces monocyte chemoattractant protein-1 gene expression in rat vascular smooth muscle cells. Chen, X.L., Tummala, P.E., Olbrych, M.T., Alexander, R.W., Medford, R.M. Circ. Res. (1998) [Pubmed]
  28. Angiotensin II is mitogenic in neonatal rat cardiac fibroblasts. Schorb, W., Booz, G.W., Dostal, D.E., Conrad, K.M., Chang, K.C., Baker, K.M. Circ. Res. (1993) [Pubmed]
  29. Regulation of angiotensin II receptor AT1 subtypes in renal afferent arterioles during chronic changes in sodium diet. Ruan, X., Wagner, C., Chatziantoniou, C., Kurtz, A., Arendshorst, W.J. J. Clin. Invest. (1997) [Pubmed]
  30. Cellular localization of AT1 receptor mRNA and protein in normal placenta and its reduced expression in intrauterine growth restriction. Angiotensin II stimulates the release of vasorelaxants. Li, X., Shams, M., Zhu, J., Khalig, A., Wilkes, M., Whittle, M., Barnes, N., Ahmed, A. J. Clin. Invest. (1998) [Pubmed]
  31. Angiotensin II inhibits insulin signaling in aortic smooth muscle cells at multiple levels. A potential role for serine phosphorylation in insulin/angiotensin II crosstalk. Folli, F., Kahn, C.R., Hansen, H., Bouchie, J.L., Feener, E.P. J. Clin. Invest. (1997) [Pubmed]
  32. Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Pitt, B., Segal, R., Martinez, F.A., Meurers, G., Cowley, A.J., Thomas, I., Deedwania, P.C., Ney, D.E., Snavely, D.B., Chang, P.I. Lancet (1997) [Pubmed]
  33. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lindholm, L.H., Ibsen, H., Dahlöf, B., Devereux, R.B., Beevers, G., de Faire, U., Fyhrquist, F., Julius, S., Kjeldsen, S.E., Kristiansson, K., Lederballe-Pedersen, O., Nieminen, M.S., Omvik, P., Oparil, S., Wedel, H., Aurup, P., Edelman, J., Snapinn, S. Lancet (2002) [Pubmed]
  34. Angiotensin II-induced hypertension increases heme oxygenase-1 expression in rat aorta. Ishizaka, N., de León, H., Laursen, J.B., Fukui, T., Wilcox, J.N., De Keulenaer, G., Griendling, K.K., Alexander, R.W. Circulation (1997) [Pubmed]
  35. Molecular cloning of a novel angiotensin II receptor isoform involved in phosphotyrosine phosphatase inhibition. Kambayashi, Y., Bardhan, S., Takahashi, K., Tsuzuki, S., Inui, H., Hamakubo, T., Inagami, T. J. Biol. Chem. (1993) [Pubmed]
  36. Essential roles for angiotensin receptor AT1a in bleomycin-induced apoptosis and lung fibrosis in mice. Li, X., Rayford, H., Uhal, B.D. Am. J. Pathol. (2003) [Pubmed]
  37. Regulation of vascular proteoglycan synthesis by angiotensin II type 1 and type 2 receptors. Shimizu-Hirota, R., Sasamura, H., Mifune, M., Nakaya, H., Kuroda, M., Hayashi, M., Saruta, T. J. Am. Soc. Nephrol. (2001) [Pubmed]
  38. Interaction of angiotensin II and mechanical stretch on vascular endothelial growth factor production by human mesangial cells. Gruden, G., Thomas, S., Burt, D., Zhou, W., Chusney, G., Gnudi, L., Viberti, G. J. Am. Soc. Nephrol. (1999) [Pubmed]
  39. Role of angiotensin II in dietary modulation of rat late distal tubule bicarbonate flux in vivo. Levine, D.Z., Iacovitti, M., Buckman, S., Burns, K.D. J. Clin. Invest. (1996) [Pubmed]
  40. Losartan and renal transplantation. Horn, S., Holzer, H., Horina, J. Lancet (1998) [Pubmed]
  41. Increase in angiotensin II type 1 receptor expression immediately after ischemia-reperfusion in isolated rat hearts. Yang, B.C., Phillips, M.I., Ambuehl, P.E., Shen, L.P., Mehta, P., Mehta, J.L. Circulation (1997) [Pubmed]
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