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Blockade of endothelial enzymes: new therapeutic targets

Journal of Human Hypertension volume 16, pages S100–S103 (2002)Cite this article

Abstract

Nitric oxide (NO) is the principal vasoactive substance produced by the vascular endothelium with antitrombotic, antiatherogenic and vasodilator actions. The loss of these functions is now known as endothelial dysfunction (ED) and it has been proposed that it is the final common pathway in cardiovascular disease. At the moment there is an important body of evidence that supports the proposal that ED is a consequence of an imbalance between the free radicals, NO, superoxide (O−2) and peroxynitrate (ONOO−). This imbalance is the result of the actions of well known risk factors associated with an inappropriate diet and infection-inflammation. Angiotensin-converting enzyme (ACE) inhibitors are highly effective against a variety of cardiovascular disorders. Experimental and clinical studies have demonstrated a beneficial effect of ACE inhibition on endothelial function. This action is mainly due to an increase in the concentration of bradykinin, which stimulates NO production. ACE inhibitors also block the formation of angiotensin II that results in a lower production of O−2. These effects lead to improve the imbalance between NO and O−2 observed in cardiovascular disease. This proposal is supported by different clinical trials that have shown that the ACE inhibitors with higher affinity by the tissular ACE, such as quinapril, are the most effective in reversing ED principally by accumulating bradykinin. Recently, the HOPE study conducted in patients at a high risk of cardiovascular events, showed how ramipril, an ACE inhibitor with high affinity by tissular ACE, decreased the mortality rate due to cardiovascular disease independently of changes in blood pressure.

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Authors and Affiliations

  1. Instituto Colombiano de Investigaciones Biomédicas (ICIB), Bucaramanga, Colombia

    P López-Jaramillo & J P Casas

  2. Universidad Industrial de Santander, Santander, Colombia

    P López-Jaramillo

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  1. P López-Jaramillo
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  2. J P Casas
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Correspondence to P López-Jaramillo.

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López-Jaramillo, P., Casas, J. Blockade of endothelial enzymes: new therapeutic targets. J Hum Hypertens 16 (Suppl 1), S100–S103 (2002). https://doi.org/10.1038/sj.jhh.1001353

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