Heart Failure Reviews

, Volume 7, Issue 4, pp 347–358 | Cite as

Angiotensin II and Nitric Oxide Interaction

  • Marc de Gasparo


Nitric oxide degradation linked to endothelial dysfunction plays a central role in cardiovascular diseases. Superoxide producing enzymes such as NADPH oxidase and xanthine oxidase are responsible for NO degradation as they generate a variety of reactive oxygen species (ROS). Moreover, superoxide is rapidly degraded by superoxide dismutase to produce hydrogen peroxide leading to the uncoupling of NO synthase and production of increased amount of superoxide.

Angiotensin II is an important stimulus of NADPH oxidase. Through its AT1 receptor, Ang II stimulates the long-term increase of several membrane component of NADPH oxidase such as P22 phox or nox-1 and causes an increased activity of NADPH oxidase with inactivation of NO leading to impaired endothelium-dependent vasorelaxation, vascular smooth muscle cell hypertrophy, proliferation and migration, extracellular matrix formation, thrombosis, cellular infiltration and inflammatory reaction. Several preclinical and clinical studies have now confirmed the involvement of the AT1 receptor in endothelial dysfunction. It is proposed that the AT2 receptor counterbalances the deleterious effect of the Ang II-induced AT1 receptor stimulation through bradykinin and NOS stimulation. This mechanism could be especially relevant in pathological cases when the NADPH oxidase activity is blocked with an AT1 receptor antagonist.

NADPH oxidase NOS superoxide oxidative stress endothelial dysfunction angiotensin receptor antagonist 


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© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Marc de Gasparo

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