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.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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.
Luscher TF, Barton M. Biology of the endothelium. Clin Cardiol. 1997;20:II-3-10.
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.
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.
Virdis A, Ghiadoni L, Versari D, et al. Endothelial function assessment in complicated hypertension. Curr Pharm Des. 2008;14:1761–70.
Lerman A, Zeiher AM. Endothelial function: cardiac events. Circulation. 2005;111:363–8.
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.
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.
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.
Tzemos N, Lim PO, MacDonald TM. Nebivolol reverses endothelial dysfunction in essential hypertension: a randomized, double-blind, crossover study. Circulation. 2001;104:511–4.
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.
Touyz RM. Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: what is the clinical significance? Hypertension. 2004;44:248–52.
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.
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.
Nishioka K, Nakagawa K, Umemura T, et al. Carvedilol improves endothelium-dependent vasodilation in patients with dilated cardiomyopathy. Heart. 2007;93:247–8.
Taddei S, Virdis A, Ghiadoni L, et al. Effects of antihypertensive drugs on endothelial dysfunction: clinical implications. Drugs. 2002;62:265–84.
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.
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.
• 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.
Ghiadoni L, Magagna A, Versari D, et al. Different effect of antihypertensive drugs on conduit artery endothelial function. Hypertension. 2003;41:1281–6.
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.
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.
Taddei S, Virdis A, Ghiadoni L, et al. Lacidipine restores endothelium-dependent vasodilation in essential hypertensive patients. Hypertension. 1997;30:1606–12.
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.
Taddei S, Virdis A, Ghiadoni L, et al. Calcium antagonist treatment by lercanidipine prevents hyperpolarization in essential hypertension. Hypertension. 2003;41:950–5.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Mimran A, Ribstein J, DuCailar G. Contrasting effect of antihypertensive treatment on the renal response to L-arginine. Hypertension. 1995;26:937–41.
Creager MA, Roddy MA. Effect of captopril and enalapril on endothelial function in hypertensive patients. Hypertension. 1994;24:499–505.
Kiowski W, Linder L, Nuesch R, et al. Effects of cilazapril on vascular structure and function in essential hypertension. Hypertension. 1996;27:371–6.
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.
Schiffrin EL. Remodeling of resistance arteries in essential hypertension and effects of antihypertensive treatment. Am J Hypertens. 2004;17:1192–200.
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.
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.
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.
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.
Benndorf RA, Appel D, Maas R, et al. Telmisartan improves endothelial function in patients with essential hypertension. J Cardiovasc Pharmacol. 2007;50:367–71.
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.
Staessen JA, Li Y, Richart T. Oral renin inhibitors. Lancet. 2006;368:1449–56.
•• 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.
Disclosure
No potential conflicts of interest relevant to this article were reported.
Author information
Authors and Affiliations
Corresponding author
Rights 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
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11906-011-0207-x