To regulate blood pressure, the brain controls circulating hormones, which influence the brain by binding to brain neurons that lie outside the blood-brain barrier. Recent work has demonstrated that "cardiovascular" hormones are synthesized and released in the brain as neurotransmitters/neuromodulators and can, in some cases, signal through the blood-brain barrier. The renin-angiotensin system is a prototype for these newly appreciated mechanisms. The brain's intrinsic renin-angiotensin system plays an important role in blood pressure control. Angiotensin II in brain neurons affects other neurons both through activation of angiotensin receptors and via generation of nitric oxide and reactive oxygen molecules. Similarly, angiotensin in blood vessels activates endothelial nitric oxide, which can diffuse across the blood-brain barrier and thereby alter neuronal activity in cardiovascular control nuclei. The relative importance of these mechanisms to blood pressure control remains to be fully elucidated. Copyright © 2008 by Current Medicine Group LLC.