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Chemical Compound Review

Cozaar     potassium[2-butyl-5-chloro-3- [[4-[2-(2,3...

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Disease relevance of losartan


Psychiatry related information on losartan


High impact information on losartan

  • This increase in DNA synthesis was abolished by the in vivo administration of an Ang II receptor-specific antagonist (DuP 753) [6].
  • We examined the effects of the AT1-receptor antagonist Losartan (DuP 753, 0.2-3.2 mg/kg) on coronary arteries in vivo in 11 dogs, using a combination of intravascular two-dimensional and Doppler ultrasound [7].
  • In addition, radioligand binding at multiple sites of transient expression of AII receptors in 2-week-old rats, including several thalamic nuclei, the nuclei of the 3rd and 12th cranial nerves, geniculate bodies, cerebellum, and cingulate cortex, was displaced by the AT2 antagonists but not by DuP 753 [8].
  • Oral administration of DuP 753, a specific angiotensin II receptor antagonist, to normal male volunteers. Inhibition of pressor response to exogenous angiotensin I and II [9].
  • Six hours after 40 mg DuP 753, the systolic blood pressure response to the test-dose of angiotensin II was reduced to 37 +/- 7%, 40 +/- 4%, and 38 +/- 6% of baseline values (mean +/- SEM, n = 6) on days 1, 4, and 8, respectively [9].

Chemical compound and disease context of losartan


Biological context of losartan

  • In marked contrast to undifferentiated cells, CGP 42112A became a potent competitor (IC50, 1 nM) for the majority (90-95%) of Ang II binding, whereas DuP 753 competed for only 5-10% of the binding sites [15].
  • Moreover, the reduction of the maximum contractile force by EXP3174 (10 nM) was concentration-dependently restored in the presence of increasing concentrations of DuP 753 (10 nM to 1 microM), indicating interaction with the same binding site [16].
  • ICV infusion of DuP 753 produced a significant increase (60 percent) in baroreflex control of heart rate in both Wistar rats and SHR [17].
  • Glomerular filtration rate was not altered by DuP 753 or captopril; however, it fell from 1.6 +/- 0.1 to 1.2 +/- 0.1 ml/min/g kidney wt during infusion of the kinin antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)[18]
  • Using this method, we demonstrated that transfection of ACE cDNA resulted in increased DNA synthesis, which was inhibited by the specific angiotensin II receptor antagonist DuP 753 (10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)[19]

Anatomical context of losartan


Associations of losartan with other chemical compounds


Gene context of losartan

  • Using the Ang II receptor subtype-selective nonpeptide antagonists, DuP 753 [selective for the type 1 Ang II (AT1) receptor] and PD 123319 [selective for the type 2 Ang II (AT2) receptor], we show that follicular granulosa cells, in vivo and in vitro, exclusively express the AT2 receptor [27].
  • By virtue of the more than 1000-fold selectivity of losartan (DuP 753) for the AT1 angiotensin II (AII) receptor subtype compared with the AT2 subtype, [3H]losartan may be a useful radioligand for studies of the AT1 receptor subtype [28].
  • Successive administration of ineffective doses of DuP 753 (losartan) and AT2 (angiotensin II) significantly decreased seizure intensity [29].
  • LY-53857 inhibited the AVP, OT, and ACTH responses to 5-HT (P<0.01), whereas DuP-753 inhibited only the AVP response (P<0.01) [30].
  • Plasma concentrations of renin and angiotensin II were increased sevenfold and 10-fold, respectively, in the rats treated with DuP 753 [31].

Analytical, diagnostic and therapeutic context of losartan


  1. Angiotensin II receptor antagonists. From discovery to antihypertensive drugs. Timmermans, P.B., Carini, D.J., Chiu, A.T., Duncia, J.V., Price, W.A., Wells, G.J., Wong, P.C., Wexler, R.R., Johnson, A.L. Hypertension (1991) [Pubmed]
  2. Angiotensin receptor regulates cardiac hypertrophy and transforming growth factor-beta 1 expression. Everett, A.D., Tufro-McReddie, A., Fisher, A., Gomez, R.A. Hypertension (1994) [Pubmed]
  3. Accupril- and Cozaar-induced angioedema in the same patient. Boxer, M. J. Allergy Clin. Immunol. (1996) [Pubmed]
  4. Cardiac haemodynamic effects of the non-peptide, angiotensin II-receptor antagonist, DuP 753, in conscious Long Evans and Brattleboro rats. Batin, P., Gardiner, S.M., Compton, A.M., Kemp, P.A., Bennett, T. Br. J. Pharmacol. (1991) [Pubmed]
  5. Differential regional haemodynamic effects of the non-peptide angiotensin II antagonist, DuP 753, in water-replete and water-deprived Brattleboro rats. Batin, P., Gardiner, S.M., Compton, A.M., Bennett, T. Life Sci. (1991) [Pubmed]
  6. Evidence for direct local effect of angiotensin in vascular hypertrophy. In vivo gene transfer of angiotensin converting enzyme. Morishita, R., Gibbons, G.H., Ellison, K.E., Lee, W., Zhang, L., Yu, H., Kaneda, Y., Ogihara, T., Dzau, V.J. J. Clin. Invest. (1994) [Pubmed]
  7. Effect of selective angiotensin II receptor antagonism and angiotensin converting enzyme inhibition on the coronary vasculature in vivo. Intravascular two-dimensional and Doppler ultrasound studies. Sudhir, K., MacGregor, J.S., Gupta, M., Barbant, S.D., Redberg, R., Yock, P.G., Chatterjee, K. Circulation (1993) [Pubmed]
  8. Differential distribution of AT1 and AT2 angiotensin II receptor subtypes in the rat brain during development. Millan, M.A., Jacobowitz, D.M., Aguilera, G., Catt, K.J. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  9. Oral administration of DuP 753, a specific angiotensin II receptor antagonist, to normal male volunteers. Inhibition of pressor response to exogenous angiotensin I and II. Christen, Y., Waeber, B., Nussberger, J., Porchet, M., Borland, R.M., Lee, R.J., Maggon, K., Shum, L., Timmermans, P.B., Brunner, H.R. Circulation (1991) [Pubmed]
  10. Characterization of PD 121981- and CGP 42112-induced unmasking of low concentration effects of angiotensin II in rabbit abdominal aorta. Hong, K.W., Rhim, B.Y., Shin, Y.W., Yoo, S.E. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  11. Hemodynamic effects of direct angiotensin II blockade compared to converting enzyme inhibition in rat model of heart failure. Raya, T.E., Fonken, S.J., Lee, R.W., Daugherty, S., Goldman, S., Wong, P.C., Timmermans, P.B., Morkin, E. Am. J. Hypertens. (1991) [Pubmed]
  12. Intracerebroventricular administration of angiotensin II increases heart rate in the conscious trout. Le Mevel, J.C., Pamantung, T.F., Mabin, D., Vaudry, H. Brain Res. (1994) [Pubmed]
  13. Anomalous effects of losartan on aminopeptidase-induced reductions of blood pressure in SHR. Wright, J.W., Hamilton, T.A., Harding, J.W. Brain Res. Bull. (1995) [Pubmed]
  14. Angiotensin II and bladder obstruction in the rat: influence on hypertrophic growth and contractility. Persson, K., Pandita, R.K., Waldeck, K., Andersson, K.E. Am. J. Physiol. (1996) [Pubmed]
  15. Identification and regulation of angiotensin II receptor subtypes on NG108-15 cells. Tallant, E.A., Diz, D.I., Khosla, M.C., Ferrario, C.M. Hypertension (1991) [Pubmed]
  16. Different types of receptor interaction of peptide and nonpeptide angiotensin II antagonists revealed by receptor binding and functional studies. Wienen, W., Mauz, A.B., Van Meel, J.C., Entzeroth, M. Mol. Pharmacol. (1992) [Pubmed]
  17. Changes in the baroreflex control of heart rate produced by central infusion of selective angiotensin antagonists in hypertensive rats. Oliveira, D.R., Santos, R.A., Santos, G.F., Khosla, M., Campagnole-Santos, M.J. Hypertension (1996) [Pubmed]
  18. Effect of an angiotensin II and a kinin receptor antagonist on the renal hemodynamic response to captopril. Fenoy, F.J., Scicli, G., Carretero, O., Roman, R.J. Hypertension (1991) [Pubmed]
  19. Novel in vitro gene transfer method for study of local modulators in vascular smooth muscle cells. Morishita, R., Gibbons, G.H., Kaneda, Y., Ogihara, T., Dzau, V.J. Hypertension (1993) [Pubmed]
  20. Depressor effect of blocking angiotensin subtype 1 receptors in anterior hypothalamus. Yang, R.H., Jin, H., Wyss, J.M., Oparil, S. Hypertension (1992) [Pubmed]
  21. Role of the renin-angiotensin system in neointima formation after injury in rabbits. Janiak, P., Libert, O., Vilaine, J.P. Hypertension (1994) [Pubmed]
  22. DuP 753 is more effective than captopril on baroreceptor function in high-renin hypertension. Moreira, E.D., Ida, F., Pires, M.D., Krieger, E.M. Hypertension (1994) [Pubmed]
  23. Novel angiotensin II antagonists distinguish amphibian from mammalian angiotensin II receptors expressed in Xenopus laevis oocytes. Ji, H., Sandberg, K., Catt, K.J. Mol. Pharmacol. (1991) [Pubmed]
  24. Hypotensive action of DuP 753, an angiotensin II antagonist, in spontaneously hypertensive rats. Nonpeptide angiotensin II receptor antagonists: X. Wong, P.C., Price, W.A., Chiu, A.T., Duncia, J.V., Carini, D.J., Wexler, R.R., Johnson, A.L., Timmermans, P.B. Hypertension (1990) [Pubmed]
  25. Central DuP 753 does not lower blood pressure in spontaneously hypertensive rats. DePasquale, M.J., Fossa, A.A., Holt, W.F., Mangiapane, M.L. Hypertension (1992) [Pubmed]
  26. Blocking hypothalamic AT1 receptors lowers blood pressure in salt-sensitive rats. Yang, R.H., Jin, H., Chen, S.J., Wyss, J.M., Oparil, S. Hypertension (1992) [Pubmed]
  27. Biochemical properties of the ovarian granulosa cell type 2-angiotensin II receptor. Pucell, A.G., Hodges, J.C., Sen, I., Bumpus, F.M., Husain, A. Endocrinology (1991) [Pubmed]
  28. Angiotensin II and non-angiotensin II displaceable binding sites for [3H]losartan in the rat liver. Grove, K.L., Speth, R.C. Biochem. Pharmacol. (1993) [Pubmed]
  29. Effects of non-peptide angiotensin II-receptor antagonists on pentylenetetrazol kindling in mice. Georgiev, V.P., Lazarova, M.B., Kambourova, T.S. Neuropeptides (1996) [Pubmed]
  30. Neuroendocrine and cardiovascular effects of serotonin: selective role of brain angiotensin on vasopressin. Saydoff, J.A., Rittenhouse, P.A., Carnes, M., Armstrong, J., Van De Kar, L.D., Brownfield, M.S. Am. J. Physiol. (1996) [Pubmed]
  31. Prolonged angiotensin II antagonism in spontaneously hypertensive rats. Hemodynamic and biochemical consequences. Bunkenburg, B., Schnell, C., Baum, H.P., Cumin, F., Wood, J.M. Hypertension (1991) [Pubmed]
  32. Regulation of aldosterone biosynthesis by adrenal renin is mediated through AT1 receptors in renin transgenic rats. Volpe, M., Rubattu, S., Gigante, B., Ganten, D., Porcellini, A., Russo, R., Romano, M., Enea, I., Lee, M.A., Trimarco, B. Circ. Res. (1995) [Pubmed]
  33. Angiotensin II and renal functional reserve in rats with Goldblatt hypertension. De Nicola, L., Keiser, J.A., Blantz, R.C., Gabbai, F.B. Hypertension (1992) [Pubmed]
  34. Role of angiotensin subtype 2 receptor in neointima formation after vascular injury. Janiak, P., Pillon, A., Prost, J.F., Vilaine, J.P. Hypertension (1992) [Pubmed]
  35. Pharmacological study of SR 47436, a non-peptide angiotensin II AT1-receptor antagonist, in conscious monkeys. Lacour, C., Roccon, A., Cazaubon, C., Segondy, D., Nisato, D. J. Hypertens. (1993) [Pubmed]
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