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Angiotensin II (Ang II) is the dominant effector of the renin-angiotensin system. In addition to its well-known hemodynamic and endocrine effects, Ang II regulates the cardiovascular remodeling associated with hypertension, atherosclerosis, heart failure, and diabetes mellitus. The importance of Ang II in cardiovascular disease states is highlighted by the prominent role that ACE inhibitors and angiotensin receptor blockers play in cardiovascular medicine. These drugs reduce clinical events and improve survival in patients with vascular disease or congestive heart failure and are among the most widely used medications in the world.1 2 There is accumulating evidence that Ang II has direct effects on smooth muscle cells (SMCs) that contribute to abnormalities ranging from subtle vascular dysfunction to severe atherosclerosis, ischemia, and necrosis. Ang II stimulates proliferation, hypertrophy, and migration of cultured vascular SMCs (VSMCs) via binding to the angiotensin type 1 (AT1) receptor.3 This receptor is a member of the superfamily of 7 transmembrane–spanning, G protein–coupled cell surface receptors (GPCRs). Traditionally, these receptors were thought to elicit intracellular signaling solely via activation of heterotrimeric G proteins, …

Role of Reactive Oxygen Species in Angiotensin II Signaling