Skip to main content
SpringerLink
Log in

The Protective Effects of Angiotensin II Blockade with Olmesartan Medoxomil on Resistance Vessel Remodeling (The VIOS study)

Rationale and Baseline Characteristics

  • Original Research Article
  • Published:
American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Background

The VIOS (Vascular Improvement with Olmesartan medoxomil Study) study is a randomized, parallel study to determine the relative effects of suppressing the renin-angiotensin system (RAS) with the angiotensin receptor antagonist olmesartan medoxomil versus suppressing sympathetic drive with the β-adrenoceptor antagonist atenolol on remodeling of the subcutaneous small resistance vessel. Remodeling of small resistance vessels may be the earliest pathologic finding associated with hypertension. It may predate the onset of clinically apparent hypertension.

Methods

In this study, 100 patients with stage I hypertension are characterized at baseline before being treated for 1 year to obtain a goal BP of less than 140/90mm Hg as defined by Joint National Committee (JNC)-7. Resistance vessel remodeling is determined using the gluteal fat biopsy technique in the hypertensive patients and a group of normotensive healthy volunteers. Additionally, efforts will be made to define whether noninvasive hemodynamic parameters, retinal vessel measurement changes, or biologic markers may predict and track the underlying vascular morphologic and physiologic changes induced by either regimen during the 12-month treatment period.

Results

The primary endpoint will be the degree of vascular remodeling as obtained from percutaneous biopsy of gluteal subcutaneous resistance vessels in each of two treatment arms compared with the normal volunteers. The design of the study and the pertinent baseline characteristics of these patients with uncomplicated essential hypertension are presented.

Conclusion

The suppression of the RAS by the blockade of angiotensin II type 1 (AT1) receptors may demonstrate remodeling effects on the ubiquitous small resistance vessels similar to that seen in the myocardium and renal glomeruli, thus affording more complete end-organ protection.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Table I
Table II
Table III
Table IV
Fig. 2

Similar content being viewed by others

References

  1. Schiffrin EL. Reactivity of small blood vessels in hypertension: relation with structural changes. State of the art lecture. Hypertension 1992 Feb; 19(2 Suppl.): II1–9

    Article  PubMed  CAS  Google Scholar 

  2. Li JS, Sharifi AM, Schiffrin EL. Effect of AT1 angiotensin-receptor blockade on structure and function of small arteries in SHR. J Cardiovasc Pharmacol 1997 Jul; 30 (1): 75–83.

    Article  PubMed  CAS  Google Scholar 

  3. Schiffrin EL, Park JB, Intengan HD, et al. Correction of arterial structure and endothelial dysfunction in human essential hypertension by the angiotensin receptor antagonist losartan. Circulation 2000 Apr 11; 101 (14): 1653–9.

    Article  PubMed  CAS  Google Scholar 

  4. Sharifi AM, Li JS, Endemann D, et al. Effects of enalapril and amlodipine on small-artery structure and composition, and on endothelial dysfunction in spontaneously hypertensive rats. J Hypertens 1998 Apr; 16 (4): 457–66.

    Article  PubMed  CAS  Google Scholar 

  5. Thybo NK, Stephens N, Cooper A, et al. Effect of antihypertensive treatment on small arteries of patients with previously untreated essential hypertension. Hypertension 1995 Apr; 25 (4 Pt 1): 474–81

    Article  PubMed  CAS  Google Scholar 

  6. Intengan HD, Deng LY, Li JS, et al. Mechanics and composition of human subcutaneous resistance arteries in essential hypertension. Hypertension 1999 Jan; 33 (1 Pt 2): 569–74

    Article  PubMed  CAS  Google Scholar 

  7. Izzard AS, Rizzoni D, Agabiti-Rosei E, et al. Small artery structure and hypertension: adaptive changes and target organ damage. J Hypertens 2005 Feb; 23 (2): 247–50.

    Article  PubMed  CAS  Google Scholar 

  8. Park JB, Charbonneau F, Schiffrin EL. Correlation of endothelial function in large and small arteries in human essential hypertension. J Hypertens 2001 Mar; 19 (3): 415–20.

    Article  PubMed  CAS  Google Scholar 

  9. Rizzoni D, Porteri E, De Ciuceis C, et al. Effect of treatment with candesartan or enalapril on subcutaneous small artery structure in hypertensive patients with noninsulin-dependent diabetes mellitus. Hypertension 2005 Apr; 45 (4): 659–65.

    Article  PubMed  CAS  Google Scholar 

  10. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003; 42(6): 1206–52

    Article  PubMed  CAS  Google Scholar 

  11. Yokoyama H, Averill DB, Brosnihan KB, et al. Role of blood pressure reduction in prevention of cardiac and vascular hypertrophy. Am J Hypertens 2005 Jul; 18 (7): 922–9.

    Article  PubMed  Google Scholar 

  12. Drazner MH, Thompson B, Rosenberg PB, et al. Comparison of impedance cardiography with invasive hemodynamic measurements in patients with heart failure secondary to ischemic or nonischemic cardiomyopathy. Am J Cardiol 2002 Apr 15; 89 (8): 993–5.

    Article  PubMed  Google Scholar 

  13. Marik PE, Pendelton JE, Smith R. A comparison of hemodynamic parameters derived from transthoracic electrical bioimpedance with those parameters obtained by thermodilution and ventricular angiography. Crit Care Med 1997 Sep; 25 (9): 1545–50.

    Article  PubMed  CAS  Google Scholar 

  14. Ventura HO, Taler SJ, Strobeck JE. Hypertension as a hemodynamic disease: the role of impedance cardiography in diagnostic, prognostic, and therapeutic decision making. Am J Hypertens 2005 Feb; 18 (2 Pt 2): 26S–43S

    Article  PubMed  Google Scholar 

  15. Cohn JN, Finkelstein S, McVeigh G, et al. Noninvasive pulse wave analysis for the early detection of vascular disease. Hypertension 1995 Sep; 26 (3): 503–8.

    Article  PubMed  CAS  Google Scholar 

  16. Zimlichman R, Shargorodsky M, Boaz M, et al. Determination of arterial compliance using blood pressure waveform analysis with the CR-2000 system: reliability, repeatability, and establishment of normal values for healthy European population. The seven European sites study (SESS). Am J Hypertens 2005 Jan; 18 (1): 65–71.

    PubMed  Google Scholar 

  17. O’Rourke MF, Pauca AL. Augmentation of the aortic and central arterial pressure waveform. Blood Press Monit 2004 Aug; 9 (4): 179–85.

    Article  PubMed  Google Scholar 

  18. Wilkinson IB, Fuchs SA, Jansen IM, et al. Reproducibility of pulse wave velocity and augmentation index measured by pulse wave analysis. J Hypertens 1998 Dec; 16 (12 Pt 2): 2079–84

    Article  PubMed  CAS  Google Scholar 

  19. Bond S, Riley WA, Barnes RW, et al. Validation studies of a noninvasive real time B-scan imaging system. In: Budinger TF, Berson AS, Ringquist I, et al., editors. Noninvasive techniques for assessment of atherosclerosis in peripheral, carotid, and coronary arteries. New York: Raven, 1982: 197–203

    Google Scholar 

  20. Yamashina A, Tomiyama H, Takeda K, et al. Validity, reproducibility, and clinical significance of noninvasive brachial-ankle pulse wave velocity measurement. Hypertens Res 2002 May; 25 (3): 359–64.

    Article  PubMed  Google Scholar 

  21. Brinchmann-Hansen O, Sandvik L. The width of the light reflex on retinal arteries and veins. Acta Ophthalmol (Copenh) 1986 Aug; 64 (4): 433–8.

    Article  CAS  Google Scholar 

  22. Dahlof B, Stenkula S, Hansson L. Hypertensive retinal vascular changes: relationship to left ventricular hypertrophy and arteriolar changes before and after treatment. Blood Press 1992 May; 1 (1): 35–44.

    Article  PubMed  CAS  Google Scholar 

  23. Herrington DM, Brosnihan KB, Pusser BE, et al. Differential effects of E and droloxifene on C-reactive protein and other markers of inflammation in healthy postmenopausal women. J Clin Endocrinol Metab 2001 Sep; 86 (9): 4216–22.

    Article  PubMed  CAS  Google Scholar 

  24. Nakamoto H, Ferrario CM, Fuller SB, et al. Angiotensin-(1–7) and nitric oxide interaction in renovascular hypertension. Hypertension 1995 Apr; 25 (4 Pt 2): 796–802

    Article  PubMed  CAS  Google Scholar 

  25. Senanayake PD, Moriguchi A, Kumagai H, et al. Increased expression of angiotensin peptides in the brain of transgenic hypertensive rats. Peptides 1994; 15(5): 919–26

    Article  PubMed  CAS  Google Scholar 

  26. Pocock SJ, McCormack V, Gueyffier F, et al. A score for predicting risk of death from cardiovascular disease in adults with raised blood pressure, based on individual patient data from randomised controlled trials. BMJ 2001 Jul 14; 323 (7304): 75–81.

    Article  PubMed  CAS  Google Scholar 

  27. Houston MC, Basile J, Bestermann WH, et al. Addressing the global cardiovascular risk of hypertension, dyslipidemia, and insulin resistance in the southeastern United States. Am J Med Sci 2005 Jun; 329 (6): 276–91.

    Article  PubMed  Google Scholar 

  28. Bianchi S, Bigazzi R, Amoroso A, et al. Silent ischemia is more prevalent among hypertensive patients with microalbuminuria and salt sensitivity. J Hum Hypertens 2003 Jan; 17 (1): 13–20.

    Article  PubMed  CAS  Google Scholar 

  29. Tomura S, Kawada K, Saito K, et al. Prevalence of microalbuminuria and relationship to the risk of cardiovascular disease in the Japanese population. Am J Nephrol 1999; 19(1): 13–20

    Article  PubMed  CAS  Google Scholar 

  30. Tomiyama H, Yamashina A, Arai T, et al. Influences of age and gender on results of noninvasive brachial-ankle pulse wave velocity measurement: a survey of 12517 subjects. Atherosclerosis 2003 Feb; 166 (2): 303–9.

    Article  PubMed  CAS  Google Scholar 

  31. McVeigh GE, Bratteli CW, Morgan DJ, et al. Age-related abnormalities in arterial compliance identified by pressure pulse contour analysis: aging and arterial compliance. Hypertension 1999 Jun; 33 (6): 1392–8.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant and study medications from Daiichi Sankyo Inc. Dr Smith has received honoraria as a member of the clinical speakers bureau of Daiichi Sankyo. The other authors declare that they have no conflicts of interest relevant to the contents of this study.

Author information

Authors and Affiliations

  1. Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Medical Center Blvd, Winston Salem, North Carolina, 27157-1032, USA

    Ronald D. Smith, Hiroshi Yokoyama, David B. Averill, Lori Cooke, K. Bridget Brosnihan & Carlos M. Ferrario

  2. Department of Medicine, Sir Mortimer B. Davis Jewish General Hospital, Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada

    Ernesto L. Schiffrin

Authors
  1. Ronald D. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroshi Yokoyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David B. Averill
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lori Cooke
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. Bridget Brosnihan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ernesto L. Schiffrin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Carlos M. Ferrario
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ronald D. Smith.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smith, R.D., Yokoyama, H., Averill, D.B. et al. The Protective Effects of Angiotensin II Blockade with Olmesartan Medoxomil on Resistance Vessel Remodeling (The VIOS study). Am J Cardiovasc Drugs 6, 335–342 (2006). https://doi.org/10.2165/00129784-200606050-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00129784-200606050-00006

Keywords

Search

Navigation