Skip to main content
Log in

Evidence for benefits of angiotensin receptor blockade beyond blood pressure control

  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Elevated levels of angiotensin II result in oxidative stress and endothelial dysfunction, which initiate atherogenic pathologic processes that are important in cardiovascular disease development. Angiotensin II induces its deleterious effects primarily through the type 1 receptor; these effects are inhibited by angiotensin II receptor blockers (ARBs) directly at the receptor level. Angiotensin II may potentiate protective mechanisms through stimulation of the type 2 receptor, which is not blocked by ARBs. Accumulating data suggest that blockade of angiotensin II production or activity provides vascular and cardioprotective benefits, such as reduction of atrial fibrillation, acute myocardial infarction, and heart failure events. Moreover, blockade of the renin-angiotensin system has been shown to offer renal protection in subjects with and without diabetes mellitus and to reduce the risk of new-onset diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Siragy HM: Angiotensin AT1 and AT2 receptors—the battle for health and disease. Nephrol Dial Transplant 2007, 22:3128–3130.

    Article  PubMed  CAS  Google Scholar 

  2. Carey RM, Siragy HM: Newly recognized components of the renin-angiotensin system: potential roles in cardiovascular and renal regulation. Endocr Rev 2003, 24:261–271.

    Article  PubMed  CAS  Google Scholar 

  3. Siragy HM, Xue C, Abadir P, Carey RM: Angiotensin subtype-2 receptors inhibit renin biosynthesis and angiotensin II formation. Hypertension 2005, 45:133–137.

    PubMed  CAS  Google Scholar 

  4. Schieffer B, Bünte C, Witte J, et al.: Comparative effects of AT1-antagonism and angiotensin-converting enzyme inhibition on markers of inflammation and platelet aggregation in patients with coronary artery disease. J Am Coll Cardiol 2004, 44:362–368.

    Article  PubMed  CAS  Google Scholar 

  5. Koh KK, Chung W-J, Ahn JY, et al.: Angiotensin II type 1 receptor blockers reduce tissue factor activity and plasminogen activator inhibitor type-1 antigen in hypertensive patients: a randomized, double-blind, placebo-controlled study. Atherosclerosis 2004, 177:155–160.

    Article  PubMed  CAS  Google Scholar 

  6. Klingbeil AU, John S, Schneider MP, et al.: AT1-receptor blockade improves augmentation index: a double-blind, randomized, controlled study. J Hypertens 2002, 20:2423–2428.

    Article  PubMed  CAS  Google Scholar 

  7. Imanishi T, Hano T, Nishio I: Angiotensin II accelerates endothelial progenitor cell senescence through induction of oxidative stress. J Hypertens 2005, 23:97–104.

    Article  PubMed  CAS  Google Scholar 

  8. Koh KK, Ahn JY, Han SH, et al.: Pleiotropic effects of angiotensin II receptor blocker in hypertensive patients. J Am Coll Cardiol 2003, 42:905–910.

    Article  PubMed  CAS  Google Scholar 

  9. Koh KK, Quon MJ, Lee Y, et al.: Additive beneficial cardiovascular and metabolic effects of combination therapy with ramipril and candesartan in hypertensive patients. Eur Heart J 2007, 28:1440–1447.

    Article  PubMed  CAS  Google Scholar 

  10. Yasunari K, Maeda K, Watanabe T, et al.: Comparative effects of valsartan versus amlodipine on left ventricular mass and reactive oxygen species formation by monocytes in hypertensive patients with left ventricular hypertrophy. J Am Coll Cardiol 2004, 43:2116–2123.

    Article  PubMed  CAS  Google Scholar 

  11. Okin PM, Devereux RB, Jern S, et al.: Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) Study Investigators: Regression of electrocardiographic left ventricular hypertrophy by losartan versus atenolol: the Losartan Intervention For Endpoint reduction in hypertension (LIFE) Study. Circulation 2003, 108:684–690.

    Article  PubMed  CAS  Google Scholar 

  12. Malmqvist K, Kahan T, Edner M, et al.: Regression of left ventricular hypertrophy in human hypertension with irbesartan. J Hypertens 2001, 19:1167–1176.

    Article  PubMed  CAS  Google Scholar 

  13. Thürmann PA, Kenedi P, Schmidt A, et al.: Influence of the angiotensin II antagonist valsartan on left ventricular hypertrophy in patients with essential hypertension. Circulation 1998, 98:2037–2042.

    PubMed  Google Scholar 

  14. Wong M, Staszewsky L, Latini R, et al.; Val-HeFT Heart Failure Trial Investigators: Valsartan benefits left ventricular structure and function in heart failure: Val-HeFT echocardiographic study. J Am Coll Cardiol 2002, 40:970–975.

    Article  PubMed  CAS  Google Scholar 

  15. Pfeffer MA, McMurray JJV, Velazquez EJ, et al.; Valsartan in Acute Myocardial Infarction Trial Investigators: Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003, 349:1893–1906.

    Article  PubMed  CAS  Google Scholar 

  16. Køber L, Torp-Pedersen C, Carlsen JE, et al.; Trandolapril Cardiac Evaluation (TRACE) Study Group: A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 1995, 333:1670–1676.

    Article  PubMed  Google Scholar 

  17. Dickstein K, Kjekshus J; OPTIMAAL Steering Committee of the OPTIMAAL Study Group: Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Lancet 2002, 360:752–760.

    Article  PubMed  CAS  Google Scholar 

  18. Cohn JN, Ferrari R, Sharpe N: Cardiac remodeling: concepts and clinical implications. A consensus paper from an international forum on cardiac remodeling. J Am Coll Cardiol 2000, 35:569–582.

    Article  PubMed  CAS  Google Scholar 

  19. Cohn JN, Tognoni G; Valsartan Heart Failure Trial Investigators: A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001, 345:1667–1675.

    Article  PubMed  CAS  Google Scholar 

  20. Pfeffer MA, Swedberg K, Granger CB, et al.; CHARM Investigators and Committees: Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003, 362:759–766.

    Article  PubMed  CAS  Google Scholar 

  21. Anand IS, Fisher LD, Chiang Y-T, et al.; Val-HeFT Investigators: Changes in brain natriuretic peptide and norepinephrine over time and mortality and morbidity in the Valsartan Heart Failure Trial (Val-HeFT). Circulation 2003, 107:1278–1283.

    Article  PubMed  CAS  Google Scholar 

  22. Cohn JN, Anand IS, Latini R, et al.; Valsartan Heart Failure Trial Investigators: Sustained reduction of aldosterone in response to the angiotensin receptor blocker valsartan in patients with chronic heart failure: results from the Valsartan Heart Failure Trial. Circulation 2003, 108:1306–1309.

    Article  PubMed  CAS  Google Scholar 

  23. Nakashima H, Kumagai K, Urata H, et al.: Angiotensin II antagonist prevents electrical remodeling in atrial fibrillation. Circulation 2000, 101:2612–2617.

    PubMed  CAS  Google Scholar 

  24. Madrid AH, Marín IM, Cervantes CE, et al.: Prevention of recurrences in patients with lone atrial fibrillation: the dose-dependent effect of angiotensin II receptor blockers. J Renin Angiotensin Aldosterone Syst 2004, 5:114–120.

    Article  PubMed  CAS  Google Scholar 

  25. López B, Querejeta R, Varo N, et al.: Usefulness of serum carboxy-terminal propeptide of procollagen type I in assessment of the cardioreparative ability of antihypertensive treatment in hypertensive patients. Circulation 2001, 104:286–291.

    PubMed  Google Scholar 

  26. Healey JS, Baranchuk A, Crystal E, et al.: Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis. J Am Coll Cardiol 2005, 45:1832–1839.

    Article  PubMed  CAS  Google Scholar 

  27. Wachtell K, Lehto M, Gerdts E, et al.: Angiotensin II receptor blockade reduces new-onset atrial fibrillation and subsequent stroke compared to atenolol: the Losartan Intervention For End Point Reduction in Hypertension (LIFE) study. J Am Coll Cardiol 2005, 45:712–719.

    Article  PubMed  CAS  Google Scholar 

  28. Maggioni A, Latini R, Carson PE, et al.: Valsartan reduces the incidence of atrial fibrillation in patients with heart failure: results from the Valsartan Heart Failure Trial (Val-HeFT). Am Heart J 2005, 149:548–557.

    Article  PubMed  CAS  Google Scholar 

  29. Jandeleit-Dahm KAM, Tikellis C, Reid CM, et al.: Why blockade of the renin-angiotensin system reduces the incidence of new-onset diabetes. J Hypertens 2005, 23:463–473.

    Article  PubMed  CAS  Google Scholar 

  30. Vijayaraghavan K, Deedwania PC: The renin angiotensin system as a therapeutic target to prevent diabetes and its complications. Cardiol Clin 2005, 23:165–183.

    Article  PubMed  Google Scholar 

  31. Shiuchi T, Iwai M, Li H-S, et al.: Angiotensin II type-1 receptor blocker valsartan enhances insulin sensitivity in skeletal muscles of diabetic mice. Hypertension 2004, 43:1003–1010.

    Article  PubMed  CAS  Google Scholar 

  32. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group: Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002, 288:2981–2997.

    Article  Google Scholar 

  33. Dahlöf B, Sever PS, Poulter NR, et al.; ASCOT Investigators: Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005, 366:895–906.

    Article  PubMed  CAS  Google Scholar 

  34. Lindholm LH, Ibsen H, Borch-Johnsen K, et al.; LIFE Study Group: Risk of new-onset diabetes in the Losartan Intervention For Endpoint reduction in hypertension study. J Hypertens 2002, 20:1879–1886.

    Article  PubMed  CAS  Google Scholar 

  35. Julius S, Kjeldsen SE, Weber M, et al.; VALUE trial group: Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004, 363:2022–2031.

    Article  PubMed  CAS  Google Scholar 

  36. Awad AS, Webb RL, Carey RM, Siragy HM: Renal nitric oxide production is decreased in diabetic rats and improved by AT1 receptor blockade. J Hypertens 2004, 22:1571–1577.

    Article  PubMed  CAS  Google Scholar 

  37. Siragy HM, Awad A, Abadir P, Webb R: The angiotensin II type 1 receptor mediates renal interstitial content of tumor necrosis factor-α in diabetic rats. Endocrinology 2003, 144:2229–2233.

    Article  PubMed  CAS  Google Scholar 

  38. Xue C, Siragy HM: Local renal aldosterone system and its regulation by salt, diabetes, and angiotensin II type 1 receptor. Hypertension 2005, 46:584–590.

    Article  PubMed  CAS  Google Scholar 

  39. Wright JT Jr, Bakris G, Greene T, et al.; African American Study of Kidney Disease and Hypertension Study Group: Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA 2002, 288:2421–2431.

    Article  PubMed  CAS  Google Scholar 

  40. Ruggenenti P, Perna A, Loriga G, et al.; REIN-2 Study Group: Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2): multicentre, randomised controlled trial. Lancet 2005, 365:939–946.

    Article  PubMed  Google Scholar 

  41. Ruggenenti P, Fassi A, Ilieva AP, et al.; Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) Investigators: Preventing microalbuminuria in type 2 diabetes. N Engl J Med 2004, 351:1941–1951.

    Article  PubMed  CAS  Google Scholar 

  42. Gupta AK, Dahlof B, Dobson J, et al.; Anglo-Scandinavian Cardiac Outcomes Trial Investigators: Determinants of new-onset diabetes among 19,257 hypertensive patients randomized in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm and the relative influence of antihypertensive medication. Diabetes Care 2008, 31:982–988.

    Article  PubMed  CAS  Google Scholar 

  43. Brenner BM, Cooper ME, de Zeeuw D, et al.; RENAAL Study Investigators: Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001, 345:861–869.

    Article  PubMed  CAS  Google Scholar 

  44. Lewis EJ, Hunsicker LG, Clarke WR, et al.; Collaborative Study Group: Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001, 345:851–860.

    Article  PubMed  CAS  Google Scholar 

  45. Parving H-H, Lehnert H, Bröchner-Mortensen J, et al.; Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group: The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001, 345:870–878.

    Article  PubMed  CAS  Google Scholar 

  46. Viberti G, Wheeldon NM; MicroAlbuminuria Reduction with VALsartan (MARVAL) Study Investigators: Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect. Circulation 2002, 106:672–678.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Helmy M. Siragy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Siragy, H.M. Evidence for benefits of angiotensin receptor blockade beyond blood pressure control. Current Science Inc 10, 261–267 (2008). https://doi.org/10.1007/s11906-008-0050-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11906-008-0050-x

Keywords

Navigation