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:

Circulating intercellular cell adhesion molecule-1, endothelin-1 and von Willebrand factor-markers of endothelial dysfunction in uncomplicated essential hypertension: the effect of treatment with ACE inhibitors

Abstract

The aim of the study was to examine whether the circulating cell adhesion molecules, von Willebrand factor (vWf) and endothelin-1, are elevated in patients with essential hypertension with no other risk factors for atherosclerosis and thus may serve as a markers of endothelial dysfunction in uncomplicated hypertension. Furthermore, the effect of treatment with the ACE inhibitor, quinapril, on levels of endothelial dysfunction markers were studied. The levels of adhesion molecules (intercellular cell adhesion molecule-1 [ICAM-1], E-selectin, P-selectin), von Wilebrand factor (vWf) and endothelin-1 were measured in patients with hypertension without any other risk factors of atherosclerosis before and after treatment with quinapril (n = 22) and in normotensive controls (n = 22). Compared with normotensive subjects, the hypertensive patients had significantly higher levels of ICAM-1 (238 vs 208 ng/ml, P = 0.02), vWf (119 vs 105 IU/dl, P < 0.05) and endothelin-1 (5.76 vs 5.14 fmol/ml, P < 0.05). Three-month treatment of hypertensive patients with quinapril led to a significant decrease in the levels of endothelin-1 (5.76 vs 5.28 fmol/ml, P < 0.01). We did not observe significant changes in the levels of adhesion molecules and vWf after ACE inhibitor treatment, although a trend toward a decrease was apparent with all these parameters. Patients with uncomplicated hypertension with no other risk factors of atherosclerosis had significantly elevated levels of ICAM-1, vWf, and endothelin-1. Our data suggest that these factors may serve as markers of endothelial damage even in uncomplicated hypertension. In hypertensive patients, treatment with the ACE inhibitor quinapril resulted in a significant decrease in endothelin-1 levels. These findings indicate a beneficial effect of ACE inhibitors on endothelial dysfunction in hypertensive patients.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Bevilacqua MP, Nelson RM . Selectins J Clin Invest 1993; 91: 379–387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ross R . The pathogenesis of atherosclerosis: a perspective for the 1990s Nature 1993; 362: 801–809

    Article  CAS  PubMed  Google Scholar 

  3. Davies MJ, Gordon JL, Gearing AJH . The expression of the adhesion molecules ICAM-1, VCAM-1 and E-selectin in human atherosclerosis J Pathol 1993; 171: 223–229

    Article  CAS  PubMed  Google Scholar 

  4. O'Brien KD et al. Neovascular expression of E-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in human atherosclerosis and their relation to intimal leucocyte content Circulation 1996; 93: 672–682

    Article  CAS  PubMed  Google Scholar 

  5. Leeuwenberg JFM et al. E-selectin and intercellular adhesion molecule-1 are released by activated human endothelial cells in vitro Immunology 1992; 77: 543–549

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Gearing AJH, Newman W . Circulating adhesion molecules in disease Immunol Today 1993; 14: 506–512

    Article  CAS  PubMed  Google Scholar 

  7. Ferri C et al. Early upregulation of endothelial adhesion molecules in obese hypertensive men Hypertension 1999; 34: 568–573

    Article  CAS  Google Scholar 

  8. Fasching P . Waldhäusl W, Wagner OF. Elevated circulating adhesion molecules in NIDDM:-potential mediators in diabetic macroangiopathy Diabetologia 1996; 39: 1242–1244

    Article  CAS  PubMed  Google Scholar 

  9. Blann AD, Tse W, Maxwell SJR, Waite MA . Increased levels of the soluble adhesion molecule E-selectin in essential hypertension J Hypertens 1994; 12: 925–928

    Article  CAS  PubMed  Google Scholar 

  10. Ferri C et al. Early activation of vascular endothelium in non-obese, non-diabetic essential hypertensivepatients with multiple metabolic abnormalities Diabetes 1998; 47: 660–667

    Article  CAS  PubMed  Google Scholar 

  11. Blann AD, Waite MA . von Willebrand factor and soluble E-selectin in hypertension: influence of treatment and value in predicting the progression of atherosclerosis Coronary Artery Dis 1996; 7: 143–147

    Article  CAS  Google Scholar 

  12. Ridker PM, Buring JE, Rifai N . Soluble P-selectin and the risk of future cardiovascular events Circulation 2001; 103: 491–495

    Article  CAS  PubMed  Google Scholar 

  13. Verhaar MC et al. Progressive vascular damage in hypertension is associated with increased levels of circulating P-selectin J Hypertens 1998; 16: 45–50

    Article  CAS  PubMed  Google Scholar 

  14. Pastore L et al. Angiotensin II stimulates intercellular adhesion molecule-1 (ICAM-1) expression by human vascular endothelial cells and increases soluble ICAM-1 release in vivo Circulation 1999; 100: 1646–1652

    Article  CAS  PubMed  Google Scholar 

  15. Krejcy K et al. Influence of angiotensin II on circulating adhesion molecules and blood leucocyte count in vivo Can J Physiol Pharmacol 1996; 74: 9–14

    Article  CAS  PubMed  Google Scholar 

  16. Dohi Y et al. Endothelin stimulated by angiotensin II augments contractility of spontaneously hypertensive rat resistance artery Hypertension 1992; 19: 131–137

    Article  CAS  PubMed  Google Scholar 

  17. Ridker PM et al. Stimulation of plasminogen activator inhibitor in vivo by infusion of angiotensin II: evidence of a potential interaction between the renin angiotensin system and fibrinolytic function Circulation 1993; 87: 1968–1973

    Article  Google Scholar 

  18. Wallén NH, Held C, Rehnqvist N, Hjemdahl P . Elevated serum intercellular adhesion molecule-1 and vascular adhesion molecule-1 amongpatients with stable angina pectoris who suffer cardiovascular death or non-fatal myocardial infarction Eur Heart J 1999; 20: 1039–1043

    Article  PubMed  Google Scholar 

  19. Ridker PM et al. Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men Lancet 1998; 351: 88–92

    Article  CAS  PubMed  Google Scholar 

  20. Fowkes FGR et al. Cross-linked fibrin degradation products, progression of peripheral arterial disease and risk of coronary heart disease Lancet 1993; 342: 84–86

    Article  CAS  PubMed  Google Scholar 

  21. Schneider MP et al. Plasma endothelin is increased in early essential hypertension Am J Hypertens 2000; 13: 579–585

    Article  CAS  PubMed  Google Scholar 

  22. Ergul A . Hypertension in blackpatients: an emerging role of endothelin system in salt sensitive hypertension Hypertension 2000; 36: 62–67

    Article  CAS  PubMed  Google Scholar 

  23. Gasic S et al. Fosinopril decreases levels of soluble vascular cell adhesion molecule-1 in borderline hypertensive type II diabeticpatients with microalbuminuria Am J Hypertens 1999; 12: 217–222

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by a grant from Internal Grant Agency, Ministry of Health of the Czech Republic No. NA/5615–3 and 64 165.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Z Hlubocká.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hlubocká, Z., Umnerová, V., Heller, S. et al. Circulating intercellular cell adhesion molecule-1, endothelin-1 and von Willebrand factor-markers of endothelial dysfunction in uncomplicated essential hypertension: the effect of treatment with ACE inhibitors. J Hum Hypertens 16, 557–562 (2002). https://doi.org/10.1038/sj.jhh.1001403

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.jhh.1001403

Keywords

This article is cited by

Search

Quick links