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:

Endothelin-1 and vasopressin plasma levels are not associated with the insertion/deletion polymorphism of the human angiotensin I-converting enzyme gene in patients with coronary artery disease

Journal of Human Hypertension volume 17, pages 133–138 (2003)Cite this article

Abstract

The objective was to investigate whether the renin–angiotensin (RA) system and related peptides endothelin-1 (ET-1) and vasopressin (VP) influence the development of coronary artery disease (CAD). Angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism has been associated with the risk of CAD. The ACE I/D polymorphism determines ACE activity, but plasma levels of other RA system components remain unchanged. However, ET-1 and VP production could be increased by RA system-dependent stimulation, continually promoted by paracrine stimulation and sustained by neointimal growth. ET-1 and VP have not been associated with the ACE I/D polymorphism so far. The present study investigated the association of the ACE I/D polymorphism with plasma concentrations of ET-1 and VP, as well as with renin, angiotensin-II (AT-II) and ACE activity in 98 Caucasian individuals with CAD. ACE I/D polymorphism showed no association with plasma levels of VP, ET-1, AT-II or renin. These parameters were also not associated taking into consideration different patient variables, such as diabetes mellitus, hypertension or severity of CAD. Only plasma ACE activity was associated with the D allele. In conclusion, the ACE I/D polymorphism could not be related to plasma concentrations of VP, ET-1, renin or AT-II, but as previously demonstrated, it could only be related to ACE activity in patients with CAD. Differences in ACE activity between ACE I/D genotype subgroups are probably compensated within the RA system itself or within non-ACE pathways, so that plasma concentrations of the related peptides ET-1 and VP remain unaffected.

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

Similar content being viewed by others

References

  1. Ertl G, Hu K . Anti-ischemic potential of drugs related to the renin–angiotensin system. J Cardiovasc Pharmacol 2001; 37 (Suppl 1): S11–S20.

    Article  CAS  Google Scholar 

  2. Unger T . Neurohormonal modulation in cardiovascular disease. Am Heart J 2000; 139: S2–S8.

    Article  CAS  Google Scholar 

  3. Luscher TF, Wenzel RR . Endothelin and endothelin antagonists: pharmacology and clinical implications. Agents Actions 1995; (Suppl): 45 237–45 253.

  4. Schiffrin EL . State-of-the-art-lecture. Role of endothelin-1 in hypertension. Hypertension 1999; 34: 876–881.

    Article  CAS  Google Scholar 

  5. Yu JCM, Davenport AP . Secretion of endothelin-1 and endothelin-3 by cultured human vascular smooth muscle cells. Br J Pharmacol 1995; 114: 551–557.

    Article  CAS  Google Scholar 

  6. Yu JCM, Davenport AP . Regulation of endothelin secretion and receptor expression in cultured vascular smooth muscle cells. J Cardiovasc Pharmacol 1995; 26 (Suppl 3): S348–S350.

    Article  CAS  Google Scholar 

  7. Al-Fakhri N, Yu JCM, Paul M, Buhr HJ . Significance of endothelin for neointima formation and neovascularization in peripheral arterial occlusive disease. Langenbecks Arch Chir 1997; (Suppl 1): 25–28.

  8. Schiffrin EL, Touyz RM . Vascular biology of endo-thelin. J Cardiovasc Pharmacol 1998; 32 (Suppl 3): S2–S13.

    CAS  Google Scholar 

  9. Lerman A et al. Circulating and tissue endothelin immunoreactivity in advanced atherosclerosis. New Engl J Med 1991; 325: 997–1001.

    Article  CAS  Google Scholar 

  10. Ihling C et al. Endothelin-1-like immunoreactivity in human atherosclerotic coronary tissue: a detailed analysis of the cellular distribution of endothelin-1. J Pathol 1996; 179: 303–308.

    Article  CAS  Google Scholar 

  11. Muders F et al. Central vasopressin is modulated by chronic blockade of the renin–angiotensin system in experimental left ventricular hypertrophy. Am J Hypertens 1999; 12: 311–314.

    Article  CAS  Google Scholar 

  12. Boldt J et al. Continuous i.v. administration of the angiotensin-converting enzyme inhibitor enalaprilat in the critically ill: effects on regulators of circulatory homeostasis. J Cardiovasc Pharmacol 1995; 25: 416–423.

    Article  CAS  Google Scholar 

  13. Rigat B et al. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990; 86: 1343–1346.

    Article  CAS  Google Scholar 

  14. Gardemann A et al. Gene polymorphism but not catalytic activity of angiotensin I-converting enzyme is associated with coronary artery disease and myocardial infarction in low-risk patients. Circulation 1995; 92: 2796–2799.

    Article  CAS  Google Scholar 

  15. Gardemann A et al. ACE I/D gene polymorphism: presence of the ACE D allele increases the risk of coronary artery disease in younger individuals. Atherosclerosis 1998; 139: 153–159.

    Article  CAS  Google Scholar 

  16. Cambien F et al. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 1992; 359: 641–644.

    Article  CAS  Google Scholar 

  17. Samani NJ et al. A meta-analysis of the association of the deletion allele of the angiotensin-converting enzyme with myocardial infarction. Circulation 1996; 94: 708–712.

    Article  CAS  Google Scholar 

  18. Lindpaintner K et al. A prospective evaluation of an angiotensin-converting enzyme gene polymorphism and the risk of ischemic heart disease. N Engl J Med 1995; 332: 706–711.

    Article  CAS  Google Scholar 

  19. Agerholm-Larsen B et al. ACE gene polymorphism: ischemic heart disease and longevity in 10 150 individuals. A case-referent and retrospective cohort study based on the Copenhagen City Heart Study. Circulation 1997; 95: 2358–2367.

    Article  CAS  Google Scholar 

  20. Lachurie ML et al. Angiotensin-converting enzyme gene polymorphism has no influence on the circulating renin–angiotensin–aldosterone system or blood pressure in normotensive subjects. Circulation 1995; 91: 2933–2942.

    Article  CAS  Google Scholar 

  21. Chadwick IG et al. Pressor and hormonal responses to angiotensin I infusion in healthy subjects of different angiotensin-converting enzyme genotypes. J Cardiovasc Pharmacol 1997; 29: 485–489.

    Article  CAS  Google Scholar 

  22. Danser AH et al. Angiotensinogen (M235T) and angiotensin-converting-enzyme (I/D) polymorphisms in association with plasma renin and prorenin levels. J Hypertens 1998; 16: 1879–1883.

    Article  CAS  Google Scholar 

  23. Tsukada K et al. Angiotensin-converting enzyme gene polymorphism and cardiovascular endocrine system in coronary angiography patients. Jpn Heart J 1997; 38: 799–810.

    Article  CAS  Google Scholar 

  24. Gensini GG . A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol 1983; 51: 606.

    Article  CAS  Google Scholar 

  25. Braunwald E et al. (eds). Harrison's Principles of Internal Medicine, 15th edn. McGraw-Hill: New York, 2001, pp 1377–1413.

    Google Scholar 

  26. Raynolds MV et al. Angiotensin-converting enzyme DD genotype in patients with ischemic or idiopathic dilated cardiomyopathy. Lancet 1993; 342: 1073–1075.

    Article  CAS  Google Scholar 

  27. Rigat B, Hubert C, Corvol P, Soubrier F . PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1). Nucleic Acids Res 1992; 20: 1433.

    Article  CAS  Google Scholar 

  28. Robertson GL, Mahr EA, Athar S, Sinha T . The development of clinical application of a new method for the radioimmunoassay of arginine vasopressin in human plasma. J Clin Invest 1973; 52: 2340–2352.

    Article  CAS  Google Scholar 

  29. Kanai H et al. Minimal daily variations of plasma and urinary endothelin-1 in healthy subjects. Clin Nephrol 1996; 46: 353–354.

    CAS  PubMed  Google Scholar 

  30. Simon D et al. Two-site direct immunoassay specific for active renin. Clin Chem 1992; 38: 1959–1962.

    CAS  PubMed  Google Scholar 

  31. Morton JJ, Webb DJ . Measurement of plasma angiotensin II. Clin Sci 1985; 68: 483–484.

    Article  CAS  Google Scholar 

  32. Beneteau B et al. Automated kinetic assay of angiotensin converting enzyme in serum. Clin Chem 1986; 32: 884–886.

    CAS  PubMed  Google Scholar 

  33. Gavras I, Gavras H . Angiotensin II as a cardiovascular risk factor. J Hum Hypertens 2002; 16 (Suppl 2): S2–S6.

    Article  CAS  Google Scholar 

  34. Vinck WJ, Fagard RH, Vlietinck R, Lijnen P . Heritability of plasma renin activity and plasma concentration of angiotensinogen and angiotensin-converting enzyme. J Hum Hypertens 2002; 16: 417–422.

    Article  CAS  Google Scholar 

  35. Davis GK, Roberts DH . Molecular genetics of the renin–angiotensin system: implications for angiotensin II receptor blockade. Pharmacol Ther 1997; 75: 43–50.

    Article  CAS  Google Scholar 

  36. McDonald JE et al. Vasoconstrictor effect of the angiotensin-converting enzyme-resistant, chymase-specific substrate [Pro(11)(D)-Ala(12)] angiotensin I in human dorsal hand veins: in vivo demonstration of non-ACE production of angiotensin II in humans. Circulation 2001; 104: 1805–1808.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank W Pabst, Institute of Medical Informatics, Justus Liebig University Giessen, for assistance with the statistical analysis employed in this study. The valuable assistance of A Hirst Ourmazd, PhD, Berlin, in the preparation of the text is gratefully acknowledged.

Author information

Author notes

  1. M Philipp

    Present address: Medical Center for Ecology, Justus Liebig University, Giessen, Germany

Authors and Affiliations

  1. Institute of Clinical Chemistry and Pathobiochemistry, Justus Liebig University, Giessen, Germany

    N Al-Fakhri, R E Linhart, M Philipp & N Katz

  2. Clinic for Cardiovascular Surgery, Justus Liebig University, Giessen, Germany

    M Heidt & F W Hehrlein

  3. Institute of Pathological Biochemistry, Otto-von-Guericke-University, Magdeburg, Germany

    A Gardemann

Authors
  1. N Al-Fakhri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R E Linhart
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Philipp
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Heidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. F W Hehrlein
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Gardemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. N Katz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N Al-Fakhri.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Al-Fakhri, N., Linhart, R., Philipp, M. et al. Endothelin-1 and vasopressin plasma levels are not associated with the insertion/deletion polymorphism of the human angiotensin I-converting enzyme gene in patients with coronary artery disease. J Hum Hypertens 17, 133–138 (2003). https://doi.org/10.1038/sj.jhh.1001519

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.jhh.1001519

Keywords

Search

Advanced search

Quick links