Abstract
Drugs that inhibit the renin–angiotensin system (RAS), namely angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor antagonists (ARA) are gaining increasing popularity as initial medications for the management of hypertensive patients. In the year 2002, ACE-I were the most commonly prescribed drugs for the treatment of hypertension in USA. Although their antihypertensive efficacy as monotherapy is similar to other antihypertensive agents, they have the advantage of better tolerability, limited side effects and a favorable metabolic profile. When compared to other antihypertensive agents (diuretics, beta-adrenergic blockers and calcium antagonists) in large clinical trials, ACE-I and ARA provided no additional advantages regarding improvement in cardiovascular and total mortality. With the exception of the superiority of ARA in prevention of stroke, RAS inhibitors have no advantage over other agents in prevention of other cardiovascular morbid events, namely, heart failure (though ACE-I are superior to calcium antagonists), coronary heart disease and total cardiovascular events. However, there is the possibility that these agents have other benefits beyond blood pressure lowering. At equal degrees of blood pressure reduction, RAS inhibitors prevent or delay the development of diabetes mellitus and provide better end-organ protection, kidneys, blood vessels and the heart when compared with other antihypertensive agents. The combined use of ACE-I and ARA is particularly useful in organ protection. RAS inhibitors are specifically indicated in the treatment of hypertension in patients with impaired left ventricular systolic function, diabetes, proteinuria, impaired kidney function, myocardial infarction, multiple cardiovascular risk factors and possibly elderly patients. The main limitation of the ACE-I is cough and rarely angioedema. Elderly patients or those who are volume depleted or receiving large doses of diuretics or in heart failure are liable to develop hypotensive reaction and/or deterioration in kidney function.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Lottermoser K, Vetter H, Düsing R . Blood pressure-independent atherogenic and thromboembolic mechanisms of the renin–angiotensin–aldosterone system. J Clin Basic Cardiol 2001; 4: 89.
Dandona P, Kumar V, Al-Jada A, Ghanim H, Syed T, Hofmayer D et al. Angiotensin II receptor blocker valsartan supresses reactive oxygen species generation in leukocytes, nuclear factor-κB, in mononuclear cells of normal subjects: evidence of an antiinflammatory action. J Clin Endocrinol Metab 2003; 88 (9): 4496–4501.
Zhuo JL . Monocyte chemoattractant protein-1: a key mediator of angiotensin II-induced target organ damage in hypertensive heart disease? J Hypertens 2004; 22: 451–454.
Nakamura S, Nakamura I, Ma L, Vaughan DE, Fogo AB . Plasminogen activator inhibitor-1 expression is regulated by the angiotensin type 1 receptor in vivo. Kidney Int 2000; 58: 251–259.
Brown NJ, Agirbasli MA, Williams GH, Litchfield WR, Vaughan DE . Effect of activation and inhibition of the renin–angiotensin system on plasma PAI-1. Hypertension 1998; 32: 965–971.
Tomiyama H, Kushiro T, Abeta H, Ishii T, Takahashi A, Furukawa L et al. Kinins contribute to the improvement of insulin sensitivity during treatment with angiotensin converting enzyme inhibitor. Hypertension 1994; 23: 450.
Gavras I, Gavras H . Angiotensin receptor blockers in the treatment of hypertension. In: Branuald E (ed.) Harrison's Advances in Cardiology. McGraw-Hill: USA, 2003, pp 75–79.
Bakris GL, Williams M, Dworkin L, Elliott WJ, Epstein M, Toto R et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis 2000; 36: 646–661.
Materson BJ, Preston RA . Angiotensin-converting enzyme inhibitors in hypertension. A dozen years of experience. Arch Intern Med 1994; 154: 513.
Neaton JD, Grimm Jr RH, Prineas RJ, Stamler J, Grandits GA, Elmer PJ et al. Treatment of mild hypertension study: final results. JAMA 1993; 270: 713.
Dickerson JE, Hingorani AD, Ashby MJ, Palmer CR, Brown MJ . Optimization of antihypertensive treatment by crossover rotation of four major classes. Lancet 1999; 353: 2008.
Materson BJ, Reda DJ, Cushman WC, Massie BM, Freis ED, Kochar MS et al. Single-drug therapy for hypertension in men. A comparison for six antihypertensive agents with placebo. N Engl J Med 1993; 328: 914.
Townsend RR, Holland OB . Combination of converting enzyme inhibitor with diuretic for the treatment of hypertension. Arch Intern Med 1990; 150: 1175.
MacGregor GA, Markandu ND, Singer DR, Furnival L, Khoshnodi L . Moderate sodium restriction with angiotensin converting enzyme inhibitors in essential hypertension: a double blind study. BMJ 1987; 294: 531.
White CM . Pharmacologic, pharmacokinetic, and therapeutic differences among ACE inhibitors. Pharmacotherapy 1998; 18: 588–599.
Zannad F, Matzinger A, Larche J . Trough/peak ratios of once daily angiotensin converting enzyme inhibitors and calcium antagnonists. Am J Hypertens 1996; 9: 633.
Frattola A, Parati G, Cuspidi C, Albini F, Mancia G . Prognostic value of 24-hour blood pressure variability. J Hypertens 1993; 11: 1133–1137.
Neutel JM . Effect of the renin–angiotensin system on the vessel wall: using ACE inhibition to improve endothelial function. J Hum Hypertens 2004; 18: 599–606.
Morgan T, Anderson A . Clinical efficacy of perindopril in hypertension. Pharmacol Physiol 1992; 19: 61–65.
Gradman A, Lewin A, Bowling BT, Tonkon M, Deedwania PC, Kezer AE et al. Comparative effect of candesartan cilexetil and losartan in patients with systemic hypertension. Heart Dis 1999; 1: 52–57.
Singer DR, Markandu ND, Shore AC, MacGregor GA . Captopril and nifedipine in combination for moderate to severe hypertension. Hypertension 1987; 9: 629–633.
Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving H-H et al for the 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 (12): 861–869.
Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB et al. 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.
Parving H-H, Hovind P, Rossing K, Andersen S . Evolving strategies for renoprotection:diabetic nephropathy. Curr Opin Nephrol Hypertens 2001; 10: 515–522.
Viberti G, Wheeldon NM, for the MARVAL Study Investigators. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus. A blood pressure independent effect. Circulation 2002; 106: 672–678.
Wright Jr JT, Bakris G, Greene T, Agodoa LY, Appel LJ, Charleston J et al. 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.
Barnett AH, Bain SC, Bouter P, Karlberg B, Madsbad S, Jervell J et al. Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med 2004; 351 (19): 1952–1962.
Ruggenenti P, Fassi A, Ilieva AP, Bruno S, Iliev IP, Brusegan V et al. Preventing microalbuminuria in type 2 diabetes. N Engl J Med 2004; 351 (19): 1941–1952.
Heart Outcomes Prevention Evaluation Study Investigators. Effects of ramipril on cardiovascular and microvascualr outcomes in people with diabetes mellitus: results of the HOPE Study and MICRO–HOPE substudy. Lancet 2000; 355: 253–259.
Ruggenenti P, Perna A, Gherardi G, Gaspari F, Benini R, Remuzzi G . Ramipril efficacy in nephropathy REIN. Lancet 1997; 349: 1875–1883.
Agodoa LY, Appel L, Bakris GL, Beck G, Bourgoignie J, Briggs JP et al. Effect of ramipril vs. amlodipine on renal outcomes in hypertensive hephrosclerosis: a randomized controlled trial. JAMA 2001; 285: 2719–2728.
Marin R, Ruilope LM, Aljama P, Aranda P, Segura J, Diez J on behalf of the investigators of the ESPIRAL Study. A random comparison of fosinopril and nifedipine GITS in patients with primary renal disease. J Hypertens 2001; 19: 1871–1876.
Parving HH, Brenner B, Cooper M, De Zeeuw D, Keane WF, Mitch WE et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861–869.
Ruggenenti P, Perna A, Mosconi L, Matalone M, Pisoni R, Gaspari F et al. Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group. Lancet 1997; 349: 1857–1863.
Mogensen CE, Neldam S, Tikkanen I, Oren S, Viskoper R, Watts RW et al. Randomized controlled trial of dual blockade of renin–angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the Candesartan and Lisinopril Microalbuminuria (CALM) study. BMJ 2000; 321: 1440–1444.
Dahlof B, Devereux R, Kjeldsen S, Beevers G, de Faire U, Fyhrquist F et al. Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet 2002; 359: 995–1003.
Lonn EM, Yusuf S, Dzavik V, Doris CI, Sabine MJ, Hutchison K et al. Effect of ramipril and vitamin E on atherosclerosis. The study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE). Circulation 2001; 103: 919–925.
Wilmink HW, Banga JD, Hijmering M, Erkelens WD, Stroes ES, Rabelink TJ . Effect of angiotensin converting enzyme inhibition in angiotensin-II type 1 receptor antagonism in postprandial endothelial function. J Am Coll Cariol 1999; 34: 104–105.
Asmar RG, Pannier B, Santoni JP, Laurent S, London GM, Levy B et al. Reversion of cardiac hypertrophy and reduced arterial compliance after converting enzyme inhibition in essential hypertension. Circulation 1988; 78: 941–950.
Thybo NK, Stephens N, Cooper A, Aalkjaer C, Heagerty AM, Mulvany MJ . Effect of antihypertensive treatment on small arteries of patients with previously untreated essential hypertension. Hypertension 1995; 25 (Part I): 474–481.
Klingbeil AU, Schneider M, Martus P, Messerli FH, Schmieder RE . A meta-analysis of the effects of treatment on left ventricular mass in essential hypertension. Am J Med 2003; 115: 41.
Cacciapouti F . Effect of ramipril and nifedipine on blood pressure and left ventricular mass index. J Cardiovasc Diagn Proc 1999; 16: 15–18.
Mogensen CE . The Kidney and Hypertension in Diabetes Mellitus, 5th edn. Kluwer Academic Publishers: Boston, MA, 2000, pp 655–706.
Hansson L, Lindholm LH, Niskanen L, Lanke J, Hedner T, Niklason A et al. Effect of angiotensin converting enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomized trial. Lancet 1999; 353: 611–616.
HOPE (Heart Outcomes Prevention Evaluation) Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000; 342: 145–153.
The EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003; 362: 782–788.
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 blockers vs diuretic. JAMA 2002; 288: 2981–2997.
The SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in a symptomatic patient with reduced left ventricular ejection fractions. N Engl J Med 1992; 327: 685–691.
Lithell H, Hansson L, Skoog I, Elmfeldt D, Hofman A, Olofsson B et al. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of randomized double-blind intervention trial. J Hypertens 2003; 21: 875–886.
Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, Hansson L et al for the VALUE trial group. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. The Lancet 2004; 363: 2022–2031.
Turnbull F, Neal B, Algert C, Chalmers J, Chapman N, Cutler J et al For the Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomized trials. Lancet 2003; 362: 1527–1535.
Wing LM, Reid CM, Ryan P, Beilin LJ, Brown MA, Jennings GL et al. A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med 2003; 348: 583–592.
Azizi M, Ménard J . Combined blockade of the renin–angiotensin system with angiotensin-converting enzyme inhibitors and angiotensin II. Type 1 receptor antagonists. Circulation 2004; 109: 2492–2499.
Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T . Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomized controlled trial. Lancet 2003; 361: 117–124.
Guidelines Committee. European Society of Hypertension–European Society of Cardiology Guidelines for the management of arterial hypertension. J Hypertens 2003; 21: 1011–1053.
Sleight P, Yusuf S . New evidence on the importance of the renin–angiotensin system in the treatment of higher-risk patients with hypertension. J Hypertens 2003; 21: 1599–1608.
Unger T . The role of rennin–angiotensin system in the development of cardiovascular disease. Am J Cardiol 2002; 89: 3A–10A.
Remme WJ, Swedberg K, Rhoon R, Teborg G, Cleland H, Hoes AW et al. For the task force for the diagnosis and treatment of chronic heart failure, European Society of Cardiology. Guidelines for the diagnosis and treatment of chronic heart failure. Eur Heart J 2001; 22: 1527–1560.
Lopez-Sendon J, Swedberg K, McMurray J, Tamargo J, Maggioni AP, Dargie H et al. For the ESC Expert Consensus document. Expert consensus document on angiotensin converting enzyme inhibitors in cardiovascular disease. The Task Force on ACE-inhibitors of the European Society of Cardiology. Eur Heart J 2004; 25: 1454–1470.
Kostis JB . The effect of enalapril on mortal and morbid events in patients with hypertension and left ventricular dysfunction. Am J Hypertens 1995; 8: 909–914.
Weber MA . The angiotensin II receptor blockers: opportunities across the spectrum of cardiovascular disease. Rev Cardiovasc Med 2002; 3: 183–191.
Yusuf S, Gerstein H, Hoogwerf B, Pogue J, Bosch J, Wolffenbuttel BH et al. Ramipril and the development of diabetes. JAMA 2001; 286: 1882.
Mitch WE . Treating diabetic nephropathy. N Engl J Med 2004; 351 (19): 1934–1937.
Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown Jr EJ, Cuddy TE et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med 1992; 327: 669–677.
Yusuf S, Pepine CJ, Garces C, Pouleur H, Salem D, Kostis J et al. Effect of enalapril on myocardial infarction and unstable angina in patients with low ejection fraction. Lancet 1992; 340: 1173–1178.
PROGRESS Collaborative Group. Randomized trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358: 1033–1041.
The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991; 325: 293–302.
Acknowledgements
We acknowledges the excellent secretarial work of Mrs Amany Kandil who helped in the typing of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ibrahim, M. RAS inhibition in hypertension. J Hum Hypertens 20, 101–108 (2006). https://doi.org/10.1038/sj.jhh.1001960
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.jhh.1001960
Keywords
This article is cited by
-
The intrarenal renin-angiotensin system in hypertension: insights from mathematical modelling
Journal of Mathematical Biology (2023)
-
M2GCN: multi-modal graph convolutional network for modeling polypharmacy side effects
Applied Intelligence (2023)
-
The use of renin angiotensin aldosterone system inhibitors may be associated with decreased mortality after cancer surgery
Scientific Reports (2022)
-
Correlation between kidney sodium and potassium handling and the renin-angiotensin-aldosterone system in children with hypertensive disorders
Pediatric Nephrology (2022)
-
Production of Dual Inhibitory Hydrolysate by Enzymatic Hydrolysis of Squid Processing By-product
Marine Biotechnology (2022)