The effect of high salt intake on endothelial function: reduced vascular nitric oxide in the absence of hypertension.

Within the last 25 years, it has become increasingly clear that high dietary salt intake represents a risk factor for the development of cardiovascular disease that is independent of its well-known ability to increase arterial pressure in some individuals. Studies in normotensive experimental animals and human subjects have revealed that a key feature of this pressure-independent effect of dietary salt is a profound reduction in vascular nitric oxide (NO) bioavailability that limits endothelium-dependent dilation. This reduction in NO is strongly associated with increased levels of reactive oxygen species (ROS) generated by NAD(P)H oxidase, xanthine oxidase or uncoupled endothelial NO synthase within the vascular wall, leading not only to scavenging of NO but also to disruption of some signaling pathways that mediate its production. The mechanistic link between high salt intake and elevated levels of enzymatically generated ROS in the peripheral vasculature is not clear, but a reduction in circulating angiotensin II may play a key role in this regard. Additional studies are needed to further elucidate the mechanisms, both at the systemic level and within the vascular wall, that trigger these salt-induced deficits in endothelial function, and to further clarify how the attendant loss of NO may disrupt tissue blood flow regulation and ultimately lead to adverse cardiovascular events.