Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

AT1-receptor blockers: differences that matter

Journal of Human Hypertension volume 16, pages S9–S16 (2002)Cite this article

Abstract

The available angiotensin II type 1 (AT1)-receptor blockers differ markedly in their pharmacological properties and clinical efficacy. Losartan shifts the dose-response curve for angiotensin II to the right without affecting the maximal response; this antagonism can be overcome by increasing concentrations of angiotensin II and thus losartan acts as a surmountable antagonist. By contrast, other agents suppress the maximal response to angiotensin II to varying extents; this can not be overcome by increasing angiotensin concentrations and hence these agents are insurmountable antagonists. Receptor binding studies have shown that candesartan has the highest affinity for the AT1-receptor, followed by irbesartan, valsartan and losartan, and that candesartan dissociates from the receptor more slowly than other antagonists. A meta-analysis using an EMax model has shown that differences in receptor binding activity are reflected in differences in maximal antihypertensive effect, and this finding is supported by the results of comparative clinical trials. Moreover, the prolonged binding of candesartan to the receptor is reflected in a longer duration of action, compared with losartan; the antihypertensive effect of candesartan persists for 48 h after dosing, compared with approximately 24 h with losartan. Candesartan thus offers extended therapeutic coverage, an important consideration since a majority of patients miss occasional doses of antihypertensive medication. There is currently no evidence that differences in receptor binding between AT1-receptor blockers translate into differences in tolerability. In summary, therefore, pharmacological differences between AT1-receptor blockers are reflected in clinically important differences in maximal antihypertensive effect, response rate, and duration of action.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Timmermans PB et al. Angiotensin II receptors and functional correlates Am J Hypertens 1992 5 (12 Pt 2): 221S–235S

    Article  Google Scholar 

  2. Dzau VJ, Sasamura H, Hein L . Heterogeneity of angiotensin synthetic pathways and receptor subtypes: physiological and pharmacological implications J Hypertens 1993 11 (Suppl): S13–S18

    Google Scholar 

  3. Booz GW, Baker KM . Role of type 1 and type 2 angiotensin receptors in angiotensin II-induced cardiomyocyte hypertrophy Hypertension 1996 28: 635–640

    Article  CAS  PubMed  Google Scholar 

  4. Ford WR, Clanachan AS, Jugdutt BI . Opposite effects of angiotensin AT1 and AT2 receptor antagonists on recovery of mechanical function after ischaemia-reperfusion in isolated working rat hearts Circulation 1996 94: 3087–3089

    Article  CAS  PubMed  Google Scholar 

  5. Johnston CI . Angiotensin II type 1 receptor blockade: a novel therapeutic concept Blood Press 2000 9 (Suppl I): 9–13

    Article  Google Scholar 

  6. Meredith PA . Clinical comparative trials of angiotensin II type 1 (AT1)-receptor blockers Blood Press 2001 10 (Suppl 3): 11–17

    Article  Google Scholar 

  7. Morsing P, Vauquelin G . How can the differences among AT1-receptor antagonists be explained? Cell Biochem Biophys 2001 35: 89–102

    Article  CAS  PubMed  Google Scholar 

  8. Vanderheyden PML, Fierens FLP, Vauquelin G . Angiotensin II type 1 receptor antagonists Why do some of them produce insurmountable inhibition? Biochem Pharmacol 2000 60: 1557–1563

    CAS  PubMed  Google Scholar 

  9. Vauquelin G, Fierens FLP, Vanderheyden PML . Distinction between surmountable and insurmountable angiotensin II AT1 receptor antagonists. In: Epstein M, Brunner HR (eds) Angiotensin II receptor antagonists Hanley & Belful: Philadelphia 2000 105–118

    Google Scholar 

  10. Morsing P et al. Mechanistic differences of various AT1-receptor blockers in isolated vessels of different origin Hypertension 1999 33: 1406–1413

    Article  CAS  PubMed  Google Scholar 

  11. Noda M et al. Inhibition of rabbit aortic angiotensin II (AII) receptor by CV-11974, a new nonpeptide AII antagonist Biochem Pharmacol 1993 46: 311–318

    Article  CAS  PubMed  Google Scholar 

  12. Fabiani ME et al. In vivo inhibition of angiotensin receptors in the rat kidney by candesartan cilexetil: a comparison with losartan Am J Hypertens 2000 13: 1005–1013

    Article  CAS  PubMed  Google Scholar 

  13. Ojima M et al. Candesartan (CV-11974) dissociates slowly from the angiotensin AT1 receptor Eur JPharmacol 1997 319: 137–146

    Article  CAS  Google Scholar 

  14. Vanderheyden PML, Fierens FLP, De Backer JP, Vauquelin G . Reversible and syntopic interaction between angiotensin receptor antagonists on Chinese hamster ovary cells expressing human angiotensin II type 1 receptors Biochem Pharmacol 2000 59: 927–935

    Article  CAS  PubMed  Google Scholar 

  15. Fierens FL, Vanderheyden PM, De Backer JP, Vauquelin G . Binding of the antagonist [3H]candesartan to angiotensin II AT1 receptor-transfected Chinese hamster ovary cells Eur J Pharmacol 1999 367: 413–422

    Article  CAS  PubMed  Google Scholar 

  16. Fierens FL, Vanderheyden PM, De Backer JP, Vauquelin G . Insurmountable angiotensin AT1 receptorantagonists: the role of tight antagonist binding Eur JPharmacol 1999 372: 199–206

    Article  CAS  Google Scholar 

  17. Azizi M, Bernard MC, Ménard J . Pharmacokinetic-pharmacodynamic study of renin release during angiotensin II blockade J Hypertens 1999 17 (Suppl 3): S195

    Google Scholar 

  18. Azizi M, Chatellier G, Guyene T-T, Ménard J . Pharmacokinetic-pharmacodynamic interactions of candesartan cilexetil and losartan J Hypertens 1999 17: 561–568

    Article  CAS  PubMed  Google Scholar 

  19. Gradman AH et al. A randomized, placebo-controlled, double-blind, parallel study of various doses of losartan potassium compared with enalapril maleate inpatients with essential hypertension Hypertension 1995 25: 1345–1350

    Article  CAS  PubMed  Google Scholar 

  20. Elmfeldt D, George M, Hübner R, Olofsson B . Candesartan cilexetil, a new generation angiotensin II antagonist, provides dose dependent antihypertensive effect J Hum Hypertens 1997 11 (Suppl 2): s49–s53

    Google Scholar 

  21. Reeves LA, Lin C-S, Kassler-Taub K, Pouleur H . Dose-related efficacy of irbesartan for hypertension. An integrated analysis Hypertension 1998 31: 1311–1316

    Article  CAS  PubMed  Google Scholar 

  22. Pool J et al. Dose-responsive antihypertensive efficacy of valsartan, a new angiotensin II-receptor blocker Clin Ther 1998 20: 1106–1114

    Article  CAS  PubMed  Google Scholar 

  23. Hansson L . The relationship between dose and antihypertensive effect for different AT1-receptor blockers Blood Press 2001 10 (Suppl 3): 33–39

    Article  Google Scholar 

  24. Andersson OK, Neldam S . The antihypertensive effect and tolerability of candesartan cilexetil, a new generation angiotensin II antagonist, in comparison with losartan Blood Press 1998 7: 53–59

    Article  CAS  PubMed  Google Scholar 

  25. Bakris G et al. Antihypertensive efficacy of candesartan in comparison to losartan: the CLAIM study J Clin Hypertens (Greenwich) 2001 3: 16–21

    Article  CAS  Google Scholar 

  26. Kassler-Taub K et al. Comparative efficacy of two angiotensin II receptor antagonists, irbesartan and losartan in mild-to-moderate hypertension. Irbesartan/ Losartan Study Investigators Am J Hypertens 1998 11 (4 Pt 1): 445–453

    Article  Google Scholar 

  27. Oparil S et al. An elective-titration study of the comparative effectiveness of two angiotensin II-receptor blockers, irbesartan and losartan. Irbesartan/Losartan Study Investigators Clin Ther 1998 20: 398–409

    Article  CAS  PubMed  Google Scholar 

  28. Hedner T et al. A comparison of the angiotensin II antagonists valsartan and losartan in the treatment of essential hypertension Am J Hypertens 1999 12 (4 Pt 1): 414–417

    Article  Google Scholar 

  29. Joint National Committee. Sixth National Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VI) Arch Intern Med 1997 157: 2413–2446

  30. Lacourcière Y, Asmar R . A comparison of the efficacy and duration of action of candesartan cilexetil and losartan as assessed by clinic and ambulatory blood pressure after a missed dose, in truly hypertensivepatients. A placebo-controlled, forced titration study Am J Hypertens 1999 12: 1181–1187

    Article  PubMed  Google Scholar 

  31. Mallion JM et al. A placebo-controlled comparison between candesartan cilexetil 8 mg and losartan 50 mg monotherapy inpatients with essential hypertension using 36H ambulatory blood pressure monitoring JRAAS 2000 1: 104

    Google Scholar 

  32. Mallion J, Siche J, Lacourcière Y . ABPM comparison of the antihypertensive profiles of the selective angiotensin II receptor antagonists telmisartan and losartan inpatients with mild-to-moderate hypertension J Hum Hypertens 1999 13: 657–664

    Article  CAS  PubMed  Google Scholar 

  33. Fogari R et al. Comparative efficacy of valsartan and losartan in mild-to-moderate hypertension: results of 24-hour ambulatory blood pressure monitoring Curr Ther Res 1999 60: 195–206

    Article  CAS  Google Scholar 

  34. Monterroso VH et al. Use of ambulatory blood pressure monitoring to compare antihypertensive efficacy and safety of two angiotensin II receptor antagonists, losartan and valsartan. Losartan Trial Investigators Adv Ther 2000 17: 117–131

    Article  CAS  PubMed  Google Scholar 

  35. Mancia G et al. Irbesartan results in superior blood pressure control vs valsartan J Hypertens 2000 18 (Suppl 2): S208

    Article  Google Scholar 

  36. Littlejohn T et al. A prospective, randomized, open-label trial comparing telmisartan 80 mg with valsartan 80 mg inpatients with mild to moderate hypertension using ambulatory blood pressure monitoring Can J Cardiol 2000 16: 1123–1132

    CAS  PubMed  Google Scholar 

  37. Rudd P et al. Issues inpatient compliance: the search for therapeutic sufficiency Cardiology 1992 80 (Suppl 1): 2–10

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiovascular Diseases, The Western Pennsylvania Hospital, Pittsburgh, Pennsylvania, USA

    A H Gradman

Authors
  1. A H Gradman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gradman, A. AT1-receptor blockers: differences that matter. J Hum Hypertens 16 (Suppl 3), S9–S16 (2002). https://doi.org/10.1038/sj.jhh.1001434

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.jhh.1001434

Keywords

This article is cited by

Search

Advanced search

Quick links