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:

Pleiotropic effects of the acute and chronic inhibition of the renin–angiotensin system in hypertensives

Journal of Human Hypertension volume 28, pages 378–383 (2014)Cite this article

Subjects

Abstract

Renin–angiotensin system (RAS) inhibition may exert beneficiary pleiotropic effects on heart hemodynamics in hypertensive patients. We aimed to assess these effects on coronary flow reserve (CFR) and left ventricular (LV) filling pressure after acute and long-term treatment. Thirty-nine patients (48.4±6.8 years) with newly diagnosed, never-treated essential arterial hypertension were consecutively recruited from an outpatient hypertension clinic. CFR in the left anterior descending artery and the ratio of mitral inflow E wave to the averaged mitral annulus tissue velocity of the E waves (E/e' ratio), as an estimate of LV filling pressure, were assessed by Doppler echocardiography. In the acute phase of the study, consecutive eligible patients were assigned to receive po Quinapril (Q) 20 mg (n=15) or Losartan (L) 100 mg (n=14) or no treatment (n=10) and were reexamined 2 h post treatment. In the chronic phase of the study, the patients were reevaluated after 1 month on the assigned treatment. During the acute phase, CFR (P=0.005) was significantly improved in the RAS inhibition as compared with the control group, independently of blood pressure (BP) changes. The E/e' ratio was also marginally improved (P=0.053), but this effect was more pronounced in patients with E/e' ratio>8 (P=0.005). CFR and E/e' ratio were also improved after 1 month of treatment, particularly in responders after the acute phase. In hypertensive patients, RAS inhibition acutely improved CFR and E/e' ratio independently of BP changes. An acute positive response in these parameters was closely related to sustained improvement after 1 month of single-drug treatment.

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

Similar content being viewed by others

References

  1. Remuzzi G, Ruggenenti P . Overview of randomised trials of ACE inhibitors. Lancet 2006; 368: 555–556.

    PubMed  Google Scholar 

  2. Jankowski P, Safar ME, Benetos A . Pleiotropic effects of drugs inhibiting the renin-angiotensin-aldosterone system. Curr Pharm Des 2009; 15: 571–584.

    Article  CAS  Google Scholar 

  3. Sanders GD, Coeytaux R, Dolor RJ, Hasselblad V, Patel UD, Powers B et al. Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), and Direct Renin Inhibitors for Treating Essential Hypertension: An Update [Internet]. Rockville (MD): Agency for Healthcare Research and Quality, 2011.

  4. Nikolaidis LA, Doverspike A, Huerbin R, Hentosz T, Shannon RP . Angiotensin-converting enzyme inhibitors improve coronary flow reserve in dilated cardiomyopathy by a bradykinin-mediated, nitric oxide-dependent mechanism. Circulation 2002; 105: 2785–2790.

    Article  CAS  Google Scholar 

  5. Aznaouridis KA, Stamatelopoulos KS, Karatzis EN, Protogerou AD, Papamichael CM, Lekakis JP . Acute effects of renin-angiotensin system blockade on arterial function in hypertensive patients. J Hum Hypertens 2007; 21: 654–663.

    Article  CAS  Google Scholar 

  6. Lethen H, Tries HP, Kersting S, Bramlage P, Lambertz H . Improvement of coronary microvascular function after Angiotensin receptor blocker treatment with irbesartan in patients with systemic hypertension. J Clin Hypertens 2011; 13: 155–161.

    Article  CAS  Google Scholar 

  7. Motz W, Strauer BE . Improvement of coronary flow reserve after long-term therapy with enalapril. Hypertension 1996; 27: 1031–1038.

    Article  CAS  Google Scholar 

  8. Schwartzkopff B, Brehm M, Mundhenke M, Strauer BE . Repair of coronary arterioles after treatment with perindopril in hypertensive heart disease. Hypertension 2000; 36: 220–225.

    Article  CAS  Google Scholar 

  9. Tomás JP, Moya JL, Barrios V, Campuzano R, Guzman G, Megías A et al. Effect of candesartan on coronary flow reserve in patients with systemic hypertension. J Hypertens 2006; 24: 2109–2114.

    Article  Google Scholar 

  10. Parodi O, Neglia D, Palombo C, Sambucenti G, Giorgetti A, Marabotti C et al. Comparative effects of enalapril and verapamil on myocardial blood flow in systemic hypertension. Circulation 1997; 96: 864–873.

    Article  CAS  Google Scholar 

  11. Cuocolo A, Storto G, Izzo R, Iovino GL, Damiano M, Bertocchi F et al. Effects of valsartan on left ventricular diastolic function in patients with mild or moderate essential hypertension: comparison with enalapril. J Hypertens 1999; 17: 1759–1766.

    Article  CAS  Google Scholar 

  12. Wachtell K, Bella JN, Rokkedal J, Palmieri V, Papademetriou V, Dahlöf B et al. Change in diastolic left ventricular filling after one year of antihypertensive treatment: The Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) Study. Circulation 2002; 105: 1071–1076.

    Article  Google Scholar 

  13. Kurland L, Hallberg P, Melhus H, Liljedahl U, Hashemi N, Syvänen AC et al. The relationship between the plasma concentration of irbesartan and the antihypertensive response is disclosed by an angiotensin II type 1 receptor polymorphism: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) Trial. Am J Hypertens 2008; 21: 836–839.

    Article  CAS  Google Scholar 

  14. Galderisi M, Cicala S, Caso P, De Simone L, D'Errico A, Petrocelli A et al. Coronary flow reserve and myocardial diastolic dysfunction in arterial hypertension. Am J Cardiol 2002; 90: 860–864.

    Article  Google Scholar 

  15. Galderisi M, de Simone G, Cicala S, De Simone L, D'Errico A, Caso P et al. Coronary flow reserve in hypertensive patients with appropriate or inappropriate left ventricular mass. J Hypertens 2003; 21: 2183–2188.

    Article  CAS  Google Scholar 

  16. Mahfouz RA, El Tahlawi MA, Ateya AA, Elsaied A . Early detection of silent ischemia and diastolic dysfunction in asymptomatic young hypertensive patients. Echocardiography 2011; 28: 564–569.

    Article  Google Scholar 

  17. Cortigiani L, Rigo F, Galderisi M, Gherardi S, Bovenzi F, Picano E et al. Diagnostic and prognostic value of Doppler echocardiographic coronary flow reserve in the left anterior descending artery. Heart 2011; 21: 1758–1765.

    Article  Google Scholar 

  18. Stewart JT, Grbic M, Sigwart U . Left atrial and left ventricular diastolic function during acute myocardial ischaemia. Br Heart J 1992; 68: 377–381.

    Article  CAS  Google Scholar 

  19. Dickerson JE, Hingorani AD, Ashby MJ, Palmer CR, Brown MJ . Optimisation of antihypertensive treatment by crossover rotation of four major classes. Lancet 1999; 353: 2008–2013.

    Article  CAS  Google Scholar 

  20. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G et al. The task force for the management of arterial hypertension of the European Society. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2007; 28: 1462.

    Google Scholar 

  21. Blood Pressure Lowering Treatment Trialists' Collaboration,, Turnbull F, Neal B, Ninomiya T, Algert C, Arima H et al. Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials. BMJ 2008; 336: 1121–1123.

    Google Scholar 

  22. Mechaeil R, Gard R, Jackson A, Rusted J . Cognitive enhancement following acute losartan in normotensive young adults. Psychopharmacology 2011; 217: 51–60.

    Article  CAS  Google Scholar 

  23. Kaufman R, Nunes I, Bolognese JA, Miller DL, Salotti D, McCarthy JM et al. Single-dose effects of isosorbide mononitrate alone or in combination with losartan on central blood pressure. J Am Soc Hypertens 2010; 4: 311–318.

    Article  CAS  Google Scholar 

  24. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA . Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol 1997; 30: 1527–1533.

    Article  CAS  Google Scholar 

  25. Saraste M, Vesalainen RK, Ylitalo A, Saraste A, Koskenvuo JW, Toikka JO et al. Transthoracic Doppler echocardiography as a noninvasive tool to assess coronary artery stenoses–a comparison with quantitative coronary angiography. J Am Soc Echocardiogr 2005; 18: 679–685.

    Article  Google Scholar 

  26. Rump AF, Rösen R, Korth A, Klaus W . Deleterious effect of exogenous angiotensin-I on the extent of regional ischaemia and its inhibition by captopril. Eur Heart J 1993; 14: 106–112.

    Article  CAS  Google Scholar 

  27. Holtz J, Busse R, Sommer O, Bassenge E . Dilation of epicardial arteries in conscious dogs induced by angiotensin-converting enzyme inhibition with enalaprilat. J Cardiovasc Pharmacol 1987; 9: 348–355.

    Article  CAS  Google Scholar 

  28. Ertl G, Hu K, Bauer WR, Bauer B . The renin-angiotensin system and coronary vasomotion. Heart 1996; 76: 45–52.

    Article  CAS  Google Scholar 

  29. Friedrich SP, Lorell BH, Rousseau MF, Hayashida W, Hess OM, Douglas PS et al. Intracardiac angiotensin-converting enzyme inhibition improves diastolic function in patients with left ventricular hypertrophy due to aortic stenosis. Circulation 1994; 90: 2761–2771.

    Article  CAS  Google Scholar 

  30. Alderman EL, Glantz SA . Acute hemodynamic interventions shift the diastolic pressure-volume curve in man. Circulation 1976; 54: 662–671.

    Article  CAS  Google Scholar 

  31. Zolk O, Flesch M, Schnabel P, Teisman AC, Pinto YM, van Gilst WH et al. Effects of quinapril, losartan and hydralazine on cardiac hypertrophy and beta-adrenergic neuroeffector mechanisms in transgenic (mREN2)27 rats. Br J Pharmacol 1998; 123: 405–412.

    Article  CAS  Google Scholar 

  32. Uchiyama-Tanaka Y, Mori Y, Kishimoto N, Fukui M, Nose A, Kijima Y et al. Comparison of the effects of quinapril and losartan on carotid artery intima-media thickness in patients with mild-to-moderate arterial hypertension. Kidney Blood Press Res 2005; 28: 111–116.

    Article  CAS  Google Scholar 

  33. Materson BJ, Reda DJ, Preston RA, Cushman WC, Massie BM, Freis ED et al. Department of veterans affairs cooperative study group on antihypertensive agents. Response to a second single antihypertensive agent used as monotherapy for hypertension after failure of the initial drug. Arch Intern Med 1995; 155: 1757.

    Article  CAS  Google Scholar 

  34. ACE Inhibitor Myocardial Infarction Collaborative Group. Indications for ACE inhibitors in the early treatment of acute myocardial infarction: systematic overview of individual data from 100,000 patients in randomized trials. Circulation 1998; 97: 2202–2212.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Therapeutics, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    K Stamatelopoulos, D Bramos, E Manios, E Alexaki, A Kaladaridou, G Georgiopoulos, E Koroboki, A Kolyviras, N Zakopoulos & S Toumanidis

  2. Department of Cardiology, Johann-Wolfgang-Goethe-University Frankfurt, Frankfurt am Main, Germany

    K Stellos

Authors
  1. K Stamatelopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D Bramos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E Manios
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E Alexaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Kaladaridou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G Georgiopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E Koroboki
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A Kolyviras
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. K Stellos
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. N Zakopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. S Toumanidis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K Stamatelopoulos.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stamatelopoulos, K., Bramos, D., Manios, E. et al. Pleiotropic effects of the acute and chronic inhibition of the renin–angiotensin system in hypertensives. J Hum Hypertens 28, 378–383 (2014). https://doi.org/10.1038/jhh.2013.125

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2013.125

Keywords

Search

Advanced search

Quick links