Angiotensin peptides and nitric oxide in cardiovascular disease.

Significance: The renin-angiotensin system (RAS) plays an important role in the normal control of cardiovascular and renal function in the healthy state and is a contributing factor in the development and progression of various types of cardiovascular diseases (CVD), including hypertension, diabetes, and heart failure.
Recent Advances: Evidence suggests that a balance between activation of the ACE/Ang II/AT1 receptor axis and the ACE2/Ang-(1-7)/Mas receptor axis is important for the function of the heart, kidney, and autonomic nervous system control of the circulation in the normal healthy state. An imbalance in these opposing pathways toward the ACE/Ang II/AT1 receptor axis is associated with CVD. The key component of this imbalance with respect to neural control of the circulation is the negative interaction between oxidative and NO• mechanisms, which leads to enhanced sympathetic tone and activation in disease conditions such as hypertension and heart failure.
Critical Issues: The key mechanisms that disrupt normal regulation of Ang II and Ang-(1-7) signaling and promote pathogenesis of CVD at all organ levels remain poorly understood. The reciprocal relation between ACE and ACE2 expression and function suggests they are controlled interdependently at pre- and post-translational levels. Insights from neural studies suggest that an interaction between oxidative and nitrosative pathways may be key.
Future Directions: The role of redox mechanisms in the control of expression and activity of RAS enzymes and Ang receptors may provide important insight into the function of local tissue RAS in health and disease.