Reactive oxygen species in the neuropathogenesis of hypertension.

New evidence that has emerged during the past several years clearly demonstrates that reactive oxygen species (ROS) in the brain play a crucial role in blood pressure regulation by serving as signaling molecules within neurons of cardiovascular control regions. In the forebrain, midbrain, and hindbrain, a key role for oxidant stress in the pathogenesis of angiotensin II-dependent and various other models of neurogenic hypertension has also been uncovered. As in the peripheral vasculature, NAD(P)H oxidase appears to be a major enzymatic source of brain ROS, and various homologues of the catalytic subunit of this enzyme appear to be differentially localized to cardiovascular-regulating nuclei in the brain. Recent studies have begun to elucidate the downstream effects of ROS in neurons, and it is now clear that ROS may interact with a number of well-described intracellular signaling pathways involved in neuronal activation. These exciting new discoveries have furthered our understanding of the pathogenesis of neurogenic hypertension and may ultimately lead to the development of new treatments. In this review, we discuss recent evidence in support of a role for brain ROS in the pathogenesis of hypertension and summarize current studies aimed at uncovering the complex mechanisms by which brain ROS regulate blood pressure in both health and cardiovascular disease.