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:

Efficacy of exercise, losartan, enalapril, atenolol and rilmenidine in subjects with blood pressure hyperreactivity at treadmill stress test and left ventricular hypertrophy

Journal of Human Hypertension volume 23, pages 259–266 (2009)Cite this article

Abstract

High levels of activity of the renin–angiotensin system (RAS) and sympathetic nervous system (SNS) are related to left ventricular hypertrophy (LVH). A percentage of subjects with hyperactivity to treadmill stress test show LVH to echocardiogram. This paper aims at evaluating neurohumoral influence over these subjects by comparing drugs that block both the RAS and the SNS. In a 1-year open protocol, 195 normotensive subjects, with hyperactivity to treadmill stress test and LVH, were randomly assigned to supervised physical exercise, rilmenidine 1 mg day−1, atenolol 50 mg day−1, enalapril 10 mg day−1 or losartan 50 mg day−1. Changes in left ventricular mass index (LVMI), measured by means of echocardiogram, were the primary end point. Changes in systolic blood pressure (SBP) at rest and peak effort were also evaluated. Enalapril significantly brought LVMI down in relation to the basal value (28.2%; n=36) similarly to losartan (26.9%; n=42); P>0.05. However, both were more efficient than physical exercise (2.9%; n=39), rilmenidine (5.1%; n=38) and atenolol (7.2%; n=40); P<0.001. There was no significant difference in SBP reduction at rest and peak effort in groups assigned to atenolol, enalapril and losartan; P>0.05. In such groups, reduction was greater than in groups assigned to physical exercise and rimenidine; P<0.001. In conclusion, drugs that block RAS were more efficient in reducing LVH than physical exercise and drugs that block SNS, and such reduction took place regardless of SBP level reduction at rest and peak effort.

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

Similar content being viewed by others

References

  1. Casale PN, Devereux RB, Milner M . Value of echocardiographic measurement of left ventricular mass in predicting cardiovascular morbid events in hypertensive men. Ann Intern Med 1986; 105: 173–178.

    Article  CAS  Google Scholar 

  2. Levy D, Garrinson RJ, Savage DB, Kannel WB, Castelli WP . Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990; 322: 1561–1566.

    Article  CAS  Google Scholar 

  3. Drayer J, Gardin J, Brewer D, Webb M . Disparate relationships between blood pressure and left ventricular mass in patients with and without left ventricular hypertrophy. Hypertension 1987; 95 (Suppl): 1161–1164.

    Google Scholar 

  4. Ren J, Hakky A, Kotler MN, Iskandrian AS . Exercise systolic blood pressure: a powerful determinant of increased left ventricular mass in patients with hypertension. J Am Coll Cardiol 1985; 5: 1224–1231.

    Article  CAS  Google Scholar 

  5. Benbassat J, Froom P . Blood pressure response to exercise as a predictor of hypertension. Arch Intern Med 1986; 146: 2053–2055.

    Article  CAS  Google Scholar 

  6. Jackson AG, Squires WG, Grimes G, Beard EF . Prediction of future resting hypertension from exercise blood pressure. J Cardiac Rehab 1983; 3: 263–268.

    Google Scholar 

  7. Gottdiener JS, Brown J, Zoltick J, Fletcher RD . Left ventricular hypertrophy in men with normal blood pressure: relation to exaggerated blood pressure response to exercise. Ann Intern Med 1990; 112: 151–156.

    Article  Google Scholar 

  8. Polônia J, Martins L, Bravo-Faria D, Macedo F, Coutinho J, Simões L . Higher left ventricle mass in normotensives with exaggerated blood pressure responses to exercise associated with higher ambulatory blood pressure load and sympathetic activity. Eur Heart J 1992; 13 (Suppl A): 30–36.

    Article  Google Scholar 

  9. Lim PO, Donnan PT, MacDonald TM . Aldosterone to renin ratio as a determinant of exercise blood pressure response in hypertensive patients. J Hum Hypertens 2001; 15: 119–123.

    Article  CAS  Google Scholar 

  10. Fagard RH, Cornelissen VA . Effect of exercise on blood pressure control in hypertensive patients. Eur J Cardiovasc Prev Rehabil 2007; 14: 12–17.

    Article  Google Scholar 

  11. Fagard RH, Cornelissen VA . Physical activity, exercise, fitness and blood pressure. In: Battagay EJ, Lip GYH, Bakris GL (eds). Hypertension: Principles and Practice. Taylor & Francis Group: Boca Raton, USA, 2005, pp 195–206.

    Chapter  Google Scholar 

  12. Higashi Y, Sasaki S, Kurisu S, Yoshimizu A, Sasaki N, Matsuura H et al. Regular aerobic exercise augments endothelium-dependent vascular relaxation in normotensive as well as hypertensive subjects. Role of endothelium-derived nitric oxide. Circulation 1999; 100: 1194–1202.

    Article  CAS  Google Scholar 

  13. The Sixth Report of the Joint National Committee on Prevention. Detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997; 157: 2413–2446.

    Article  Google Scholar 

  14. Bruce RA, Blackman JR, Jones JW . Exercise testing in adult normal subjects and cardiac patients. Pediatrics 1963; 32: 742–755.

    Google Scholar 

  15. Astrand PO, Rhyming I . Normogram for calculation of aerobics capacity (physical fitness) from pulse during submaximal work. J Appl Physiol 1954; 71: 218–221.

    Article  Google Scholar 

  16. Bhanbhani Y, Buckley S, Maikala R . Physiological and biomechanical responses during treadmill walking with graded loads. Eur J Appl Physiol 1997; 76: 544–551.

    Article  Google Scholar 

  17. Froelicher Jr VF, Brammell H, Davis G . A comparison of the reproducibility and physiologic responses to three maximal treadmill exercise protocols. Chest 1974; 65: 512–517.

    Article  Google Scholar 

  18. Harrison MH, Brown GA, Cochran L . Maximal oxygen uptake: its measurement application, and limitations. Aviat Space Environ Med 1980; 51: 1123–1127.

    CAS  PubMed  Google Scholar 

  19. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campos E, Sachs I et al. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986; 57: 450–458.

    Article  CAS  Google Scholar 

  20. Sharabi Y, Ben-Cnaan R, Hanin A, Martonovitch G, Grossman E . The significance of hypertensive response to exercise as a predictor of hypertension and cardiovascular disease. J Hum Hypertens 2001; 15: 353–356.

    Article  CAS  Google Scholar 

  21. Wilson NV, Meyer BM . Early prediction of hypertension using exercise blood pressure. Prev Med 1981; 10: 62–68.

    Article  CAS  Google Scholar 

  22. Wilson MF, Sung BH, Pincomb GA, Lovallo WR . Exaggerated pressure response to exercise in men at risk for systemic hypertension. Am J Cardiol 1990; 66: 731–736.

    Article  CAS  Google Scholar 

  23. Dlin RA, Hanne N, Silverberg DS, Bar-or O . Follow-up of normotensive men with exaggerated blood pressure response to exercise. Am Heart J 1983; 106: 316–320.

    Article  CAS  Google Scholar 

  24. Michelsen S, Knutsen KM, Stugaard M, Otterstad JE . Is left ventricular mass in apparently healthy normotensive men correlated to maximal blood pressure during exercise? Eur Heart J 1990; 11: 241–248.

    Article  CAS  Google Scholar 

  25. Schimider RE, Martus P, Klingbeil A . Reversal of left ventricular hypertrophy in essential hypertension: a meta analysis of randomized double-blind studies. JAMA 1996; 275: 1507–1513.

    Article  Google Scholar 

  26. Jennings G, Wong J . Regression of left ventricular hypertrophy: changing patterns with successive meta-analyses. J Hypertens 1998; 16 (Suppl 6): S29–S34.

    CAS  Google Scholar 

  27. Somers VK, Conway J, Johnston J, Sleight P . Effects of endurance training on baroreflex sensitivity and blood pressure in borderline hypertension. Lancet 1991; 337: 1363–1368.

    Article  CAS  Google Scholar 

  28. Grassi G, Seravalle G, Calhoun AD, Mancia G . Physical training and baroreceptor control of sympathetic nerve activity in humans. Hypertension 1994; 23: 294–301.

    Article  CAS  Google Scholar 

  29. Parrault H, Peronnet F, Cleroux J, Consineau D, Nadeau R, Phan Hey H et al. Electro- and echocardiographic assessment of left ventricle before and after training man. Can J Appl Sports Sci 1978; 3: 180–182.

    Google Scholar 

  30. Wolfe LA, Martin RP, Watson DD, Lasley RD, Bruns DE . Chronic exercise and left ventricular structure and function in healthy human subjects. J Appl Physiol 1985; 58: 409–415.

    Article  CAS  Google Scholar 

  31. Cuspidi C, Muiesan ML, Valagussa L, Salvetti M, Di Biagio C, Zanchetti A et al. Comparative effects of candesartan and enalapril on left ventricular hypertrophy in patients with essential hypertension: The Candesartan Assessment in the Treatment of Cardiac Hypertrophy (CATCH) study. J Hypertens 2002; 20: 2293–2300.

    Article  CAS  Google Scholar 

  32. Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, Faire UD 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.

    Article  Google Scholar 

  33. Trimarco B, Morisco C, Sarmo D, Iovino G, Argenziano L, Russo R . Rilmenidine in patients with left ventricular hypertrophy: beyond the reduction of left ventricular mass. J Cardiovasc Pharmacol 1995; 26 (Suppl 2): S29–S33.

    Article  CAS  Google Scholar 

  34. Goodfriend TI, Elliot ME, Catt KJ . Angiotensin receptors and their antagonists. N Engl J Med 1996; 334: 1649–1654.

    Article  CAS  Google Scholar 

  35. Kopin IJ . Catecholamine metabolism: basic aspects and clinical significance. Pharmacol Rev 1985; 37: 333–364.

    CAS  PubMed  Google Scholar 

  36. Goldstein DS . The Autonomic Nervous System in Health and Disease. Marcel Dekker, Inc.: New York, NY, 2001.

    Google Scholar 

  37. Brown EJ, Schreiber SL . A signaling pathway to translational control. Cell 1996; 86: 517–520.

    Article  CAS  Google Scholar 

  38. Fossum E, Olsen MH, Hoieggen A, Wachtell K, Reins HM, Ibsen H et al. Long-term plasma catecholamines in patients with hypertension and left ventricular hypertrophy treated with losartan or atenolol: ICASUS, a LIFE substudy. J Hum Hypertens 2004; 18: 375–380.

    Article  CAS  Google Scholar 

  39. Schunkert H, Hence HW, Holmer SR, Stender M, Perz S, Keil V et al. Association between a deletion polymorphism of angiotensin-converting enzyme gene and left ventricular hypertrophy. N Engl J Med 1994; 330: 1634–1638.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the Alquimia Drugstores for donation of all drugs used in the study; The Espirito Santo Hospital Military Police, where patients were attended to and complementary examinations were carried out; and the Heart Institute (InCor), University of São Paulo Medical School for all technical support required for the accomplishment of this study.

Author information

Authors and Affiliations

  1. Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina do Estado de São Paulo, São Paulo, Brazil

    A C Avanza Jr, A P Mansur & J A F Ramires

Authors
  1. A C Avanza Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A P Mansur
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J A F Ramires
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A P Mansur.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Avanza, A., Mansur, A. & Ramires, J. Efficacy of exercise, losartan, enalapril, atenolol and rilmenidine in subjects with blood pressure hyperreactivity at treadmill stress test and left ventricular hypertrophy. J Hum Hypertens 23, 259–266 (2009). https://doi.org/10.1038/jhh.2008.127

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2008.127

Keywords

Search

Advanced search

Quick links