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Targeting endothelial dysfunction in hypertensive subjects

Abstract

The endothelium is a favourite early target of cardiovascular risk factors and cardiovascular diseases like hypertension. This key role of the endothelium results from its capacity to respond to numerous autocrine and paracrine stimuli and to mechanical factors like shear stress but also from the pathophysiological consequences of endothelial dysfunction on vasomotor tone, arterial stiffness, arterial remodelling, and inflammation, all of which are factors that play a critical role in atherosclerosis and target-organ damage. In hypertension, endothelial dysfunction has been shown at the level of both resistance and conduit arteries and mainly results from an increase in nitric oxide (NO) degradation by interaction between NO and superoxide anions, while in experimental models of hypertension a decrease in NO production can also be observed. The fact that forearm endothelial dysfunction is a marker of future cardiovascular events in patients with hypertension stresses the importance of the clinical evaluation of endothelial function and of the evaluation of the effects of the different antihypertensive drug classes on this parameter. In this context, many studies have demonstrated that angiotensin-converting enzyme inhibitors, the perindopril–indapamide combination, and angiotensin II type I receptor (AT1) blockers improve endothelium-dependent vasodilatation partly independently of arterial pressure. Both their antioxidant effects and the stimulation of the release of NO are involved in their beneficial effects. For calcium antagonists, only the recent drugs have been shown to improve endothelial function with a simultaneous improvement in several markers of oxidative stress. Finally, β-blockers classically do not affect endothelial function. Only nebivolol, a β-blocker with NO donor properties, has been shown to improve endothelial function, but this effect results from the increase in NO and not from the β-blocking properties of the drug.

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Correspondence to C Thuillez.

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Thuillez, C., Richard, V. Targeting endothelial dysfunction in hypertensive subjects. J Hum Hypertens 19 (Suppl 1), S21–S25 (2005). https://doi.org/10.1038/sj.jhh.1001889

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  • DOI: https://doi.org/10.1038/sj.jhh.1001889

Keywords

  • endothelium
  • hypertension
  • antihypertensive drugs
  • converting enzyme inhibitors
  • diuretics

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