The Pickering Lecture British Hypertension Society, 10th September 2002

An elevation in angiotensin II (Ang II) levels is a common occurrence in a diverse number of cardiovascular diseases including hypertension, hypercholesterolaemia, atherosclerotic coronary artery disease, left ventricular hypertrophy (LVH), heart failure and diabetes. An important effect of Ang II is activation of the NAD(P)H oxidase, a major source of reactive oxygen species (ROS) production by vascular cells. This increase in cellular ROS contributes to the pathogenesis of vascular disease by altering endothelial cell function, enhancing smooth muscle cell growth and proliferation, stimulating inflammatory proteins, including macrophage chemoattractant agents, growth factors and cytokines, and modulating matrix remodelling. Studies of genetically-altered mice have unequivocally shown that activation of the NAD(P)H oxidase by Ang II contributes to hypertension, LVH and atherosclerosis. Furthermore, increasing evidence suggest that the NAD(P)H oxidase contributes to human disease, suggesting that it is a potential target for future therapeutic intervention.