Skip to main content
Log in

Effects of Antihypertensive Treatment on Endothelial Function

  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Essential hypertension is characterized by endothelial dysfunction due to reduced availability of nitric oxide (NO) secondary to increased generation of oxygen-free radicals. Some antihypertensive drugs may improve or restore endothelial function independently of their blood pressure lowering effect. The newer generation of β-blockers, such as nebivolol and carvedilol, which provide antioxidant activity, can improve endothelial function in patients with hypertension. Dihydropyridine and non-dihydropyridine calcium antagonists reverse impaired endothelium-dependent vasodilatation in different vascular districts, through a mechanism related to an antioxidant effect. However, conflicting results are found in the brachial artery. Angiotensin-converting enzyme (ACE) inhibitors improve endothelial function in subcutaneous, epicardial, brachial, and renal circulation, but they are ineffective in potentiating the impaired response to acetylcholine in the forearm of hypertensive patients. Angiotensin II receptor antagonists can restore endothelium-dependent vasodilatation to acetylcholine in subcutaneous microcirculation but not in that of the forearm muscle. They also improve basal NO release and decrease the vasoconstrictor effect of endogenous endothelin-1. Large-scale clinical trials are required to definitively demonstrate that treatment of endothelial dysfunction can improve the prognosis of patients with essential hypertension.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Taddei S, Ghiadoni L, Virdis A, et al. Mechanisms of endothelial dysfunction: clinical significance and preventive non-pharmacological therapeutic strategies. Curr Pharm Des. 2003;9:2385–402.

    Article  PubMed  CAS  Google Scholar 

  2. Luscher TF, Barton M. Biology of the endothelium. Clin Cardiol. 1997;20:II-3-10.

    Google Scholar 

  3. Taddei S, Virdis A, Ghiadoni L, et al. Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension. Circulation. 1998;97:2222–9.

    PubMed  CAS  Google Scholar 

  4. Solzbach U, Hornig B, Jeserich M, et al. Vitamin C improves endothelial dysfunction of epicardial coronary arteries in hypertensive patients. Circulation. 1997;96:1513–9.

    PubMed  CAS  Google Scholar 

  5. Virdis A, Ghiadoni L, Versari D, et al. Endothelial function assessment in complicated hypertension. Curr Pharm Des. 2008;14:1761–70.

    Article  PubMed  CAS  Google Scholar 

  6. Lerman A, Zeiher AM. Endothelial function: cardiac events. Circulation. 2005;111:363–8.

    Article  PubMed  Google Scholar 

  7. Schiffrin EL, Deng LY. Structure and function of resistance arteries of hypertensive patients treated with a beta-blocker or a calcium channel antagonist. J Hypertens. 1996;14:1247–55.

    Article  PubMed  CAS  Google Scholar 

  8. Taddei S, Virdis A, Ghiadoni L, et al. Effect of calcium antagonist or beta blockade treatment on nitric oxide-dependent vasodilation and oxidative stress in essential hypertensive patients. J Hypertens. 2001;19:1379–86.

    Article  PubMed  CAS  Google Scholar 

  9. Cockcroft JR, Chowienczyk PJ, Brett SE, et al. Nebivolol vasodilates human forearm vasculature: evidence for an L-arginine/NO-dependent mechanism. J Pharmacol Exp Ther. 1995;274:1067–71.

    PubMed  CAS  Google Scholar 

  10. Tzemos N, Lim PO, MacDonald TM. Nebivolol reverses endothelial dysfunction in essential hypertension: a randomized, double-blind, crossover study. Circulation. 2001;104:511–4.

    Article  PubMed  CAS  Google Scholar 

  11. Mason RP, Kubant R, Jacob RF, et al. Effect of nebivolol on endothelial nitric oxide and peroxynitrite release in hypertensive animals: role of antioxidant activity. J Cardiovasc Pharmacol. 2006;48:862–9.

    Article  PubMed  CAS  Google Scholar 

  12. Touyz RM. Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: what is the clinical significance? Hypertension. 2004;44:248–52.

    Article  PubMed  CAS  Google Scholar 

  13. Feuerstein GZ, Ruffolo Jr RR. Carvedilol, a novel multiple action antihypertensive agent with antioxidant activity and the potential for myocardial and vascular protection. Eur Heart J. 1995;16(Suppl F):38–42.

    PubMed  CAS  Google Scholar 

  14. Bank AJ, Kelly AS, Thelen AM, et al. Effects of carvedilol versus metoprolol on endothelial function and oxidative stress in patients with type 2 diabetes mellitus. Am J Hypertens. 2007;20:777–83.

    Article  PubMed  CAS  Google Scholar 

  15. Nishioka K, Nakagawa K, Umemura T, et al. Carvedilol improves endothelium-dependent vasodilation in patients with dilated cardiomyopathy. Heart. 2007;93:247–8.

    Article  PubMed  CAS  Google Scholar 

  16. Taddei S, Virdis A, Ghiadoni L, et al. Effects of antihypertensive drugs on endothelial dysfunction: clinical implications. Drugs. 2002;62:265–84.

    Article  PubMed  CAS  Google Scholar 

  17. Frielingsdorf J, Seiler C, Kaufmann P, et al. Normalization of abnormal coronary vasomotion by calcium antagonists in patients with hypertension. Circulation. 1996;93:1380–7.

    PubMed  CAS  Google Scholar 

  18. Effect of nifedipine and cerivastatin on coronary endothelial function in patients with coronary artery disease: the ENCORE I Study (Evaluation of Nifedipine and Cerivastatin On Recovery of coronary Endothelial function). Circulation. 2003;107:422–8.

  19. • Luscher TF, Pieper M, Tendera M, et al. A randomized placebo-controlled study on the effect of nifedipine on coronary endothelial function and plaque formation in patients with coronary artery disease: the ENCORE II study. Eur Heart J. 2009;30:1590–7. This study demonstrates in a multicenter setting that calcium channel blockade with nifedipine for up to 2 years improves coronary endothelial function.

    Article  PubMed  Google Scholar 

  20. Ghiadoni L, Magagna A, Versari D, et al. Different effect of antihypertensive drugs on conduit artery endothelial function. Hypertension. 2003;41:1281–6.

    Article  PubMed  CAS  Google Scholar 

  21. Muiesan ML, Salvetti M, Monteduro C, et al. Effect of treatment on flow-dependent vasodilation of the brachial artery in essential hypertension. Hypertension. 1999;33:575–80.

    PubMed  CAS  Google Scholar 

  22. Corretti MC, Anderson TJ, Benjamin EJ, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002;39:257–65.

    Article  PubMed  Google Scholar 

  23. Taddei S, Virdis A, Ghiadoni L, et al. Lacidipine restores endothelium-dependent vasodilation in essential hypertensive patients. Hypertension. 1997;30:1606–12.

    PubMed  CAS  Google Scholar 

  24. Sudano I, Virdis A, Taddei S, et al. Chronic treatment with long-acting nifedipine reduces vasoconstriction to endothelin-1 in essential hypertension. Hypertension. 2007;49:285–90.

    Article  PubMed  CAS  Google Scholar 

  25. Taddei S, Virdis A, Ghiadoni L, et al. Calcium antagonist treatment by lercanidipine prevents hyperpolarization in essential hypertension. Hypertension. 2003;41:950–5.

    Article  PubMed  CAS  Google Scholar 

  26. Perticone F, Ceravolo R, Maio R, et al. Calcium antagonist isradipine improves abnormal endothelium-dependent vasodilation in never treated hypertensive patients. Cardiovasc Res. 1999;41:299–306.

    Article  PubMed  CAS  Google Scholar 

  27. Versari D, Virdis A, Ghiadoni L, et al. Effect of verapamil, trandolapril and their combination on vascular function and structure in essential hypertensive patients. Atherosclerosis. 2009;205:214–20.

    Article  PubMed  CAS  Google Scholar 

  28. Mak IT, Boehme P, Weglicki WB. Antioxidant effects of calcium channel blockers against free radical injury in endothelial cells. Correlation of protection with preservation of glutathione levels. Circ Res. 1992;70:1099–103.

    PubMed  CAS  Google Scholar 

  29. Taddei S, Virdis A, Ghiadoni L, et al. Restoration of nitric oxide availability after calcium antagonist treatment in essential hypertension. Hypertension. 2001;37:943–8.

    PubMed  CAS  Google Scholar 

  30. Virdis A, Neves MF, Amiri F, et al. Role of NAD(P)H oxidase on vascular alterations in angiotensin II-infused mice. J Hypertens. 2004;22:535–42.

    Article  PubMed  CAS  Google Scholar 

  31. Virdis A, Colucci R, Fornai M, et al. Cyclooxygenase-1 is involved in endothelial dysfunction of mesenteric small arteries from angiotensin II-infused mice. Hypertension. 2007;49:679–86.

    Article  PubMed  CAS  Google Scholar 

  32. Schiffrin EL, Deng LY. Comparison of effects of angiotensin I-converting enzyme inhibition and beta-blockade for 2 years on function of small arteries from hypertensive patients. Hypertension. 1995;25:699–703.

    PubMed  CAS  Google Scholar 

  33. Rizzoni D, Muiesan ML, Porteri E, et al. Effects of long-term antihypertensive treatment with lisinopril on resistance arteries in hypertensive patients with left ventricular hypertrophy. J Hypertens. 1997;15:197–204.

    Article  PubMed  CAS  Google Scholar 

  34. Antony I, Lerebours G, Nitenberg A. Angiotensin-converting enzyme inhibition restores flow-dependent and cold pressor test-induced dilations in coronary arteries of hypertensive patients. Circulation. 1996;94:3115–22.

    PubMed  CAS  Google Scholar 

  35. Mancini GB, Henry GC, Macaya C, et al. Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND (Trial on Reversing ENdothelial Dysfunction) Study. Circulation. 1996;94:258–65.

    PubMed  CAS  Google Scholar 

  36. Anderson TJ, Elstein E, Haber H, et al. Comparative study of ACE-inhibition, angiotensin II antagonism, and calcium channel blockade on flow-mediated vasodilation in patients with coronary disease (BANFF study). J Am Coll Cardiol. 2000;35:60–6.

    Article  PubMed  CAS  Google Scholar 

  37. Ghiadoni L, Versari D, Magagna A, et al. Ramipril dose-dependently increases nitric oxide availability in the radial artery of essential hypertension patients. J Hypertens. 2007;25:361–6.

    Article  PubMed  CAS  Google Scholar 

  38. Mimran A, Ribstein J, DuCailar G. Contrasting effect of antihypertensive treatment on the renal response to L-arginine. Hypertension. 1995;26:937–41.

    PubMed  CAS  Google Scholar 

  39. Creager MA, Roddy MA. Effect of captopril and enalapril on endothelial function in hypertensive patients. Hypertension. 1994;24:499–505.

    PubMed  CAS  Google Scholar 

  40. Kiowski W, Linder L, Nuesch R, et al. Effects of cilazapril on vascular structure and function in essential hypertension. Hypertension. 1996;27:371–6.

    PubMed  CAS  Google Scholar 

  41. Taddei S, Virdis A, Ghiadoni L, et al. Effects of angiotensin converting enzyme inhibition on endothelium-dependent vasodilatation in essential hypertensive patients. J Hypertens. 1998;16:447–56.

    Article  PubMed  CAS  Google Scholar 

  42. Schiffrin EL. Remodeling of resistance arteries in essential hypertension and effects of antihypertensive treatment. Am J Hypertens. 2004;17:1192–200.

    Article  PubMed  CAS  Google Scholar 

  43. 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;45:659–65.

    Article  PubMed  CAS  Google Scholar 

  44. 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;101:1653–9.

    PubMed  CAS  Google Scholar 

  45. Ghiadoni L, Virdis A, Magagna A, et al. Effect of the angiotensin II type 1 receptor blocker candesartan on endothelial function in patients with essential hypertension. Hypertension. 2000;35:501–6.

    PubMed  CAS  Google Scholar 

  46. Bellien J, Iacob M, Eltchaninoff H, et al. AT1 receptor blockade prevents the decrease in conduit artery flow-mediated dilatation during NOS inhibition in humans. Clin Sci (Lond). 2007;112:393–401.

    Article  CAS  Google Scholar 

  47. Benndorf RA, Appel D, Maas R, et al. Telmisartan improves endothelial function in patients with essential hypertension. J Cardiovasc Pharmacol. 2007;50:367–71.

    Article  PubMed  CAS  Google Scholar 

  48. Hornig B, Landmesser U, Kohler C, et al. Comparative effect of ace inhibition and angiotensin II type 1 receptor antagonism on bioavailability of nitric oxide in patients with coronary artery disease: role of superoxide dismutase. Circulation. 2001;103:799–805.

    PubMed  CAS  Google Scholar 

  49. Staessen JA, Li Y, Richart T. Oral renin inhibitors. Lancet. 2006;368:1449–56.

    Article  PubMed  CAS  Google Scholar 

  50. •• Imanishi T, Tsujioka H, Ikejima H, et al. Renin inhibitor aliskiren improves impaired nitric oxide bioavailability and protects against atherosclerotic changes. Hypertension. 2008;52:563–72. This elegant study represents the first demonstration in animals that aliskiren may ameliorate endothelial function and protect the vasculature against atherosclerosis.

    Article  PubMed  CAS  Google Scholar 

Download references

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stefano Taddei.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Virdis, A., Ghiadoni, L. & Taddei, S. Effects of Antihypertensive Treatment on Endothelial Function. Curr Hypertens Rep 13, 276–281 (2011). https://doi.org/10.1007/s11906-011-0207-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11906-011-0207-x

Keywords

Navigation