Salt, Angiotensin II, Superoxide, and Endothelial Function

Abstract

Proper function of the vascular endothelium is essential for cardiovascular health, in large part due to its antiproliferative, antihypertrophic, and anti-inflammatory properties. Crucial to the protective role of the endothelium is the production and liberation of nitric oxide (NO), which not only acts as a potent vasodilator, but also reduces levels of reactive oxygen species, including superoxide anion (O2•-). Superoxide anion is highly injurious to the vasculature because it not only scavenges NO molecules, but has other damaging effects, including direct oxidative disruption of normal signaling mechanisms in the endothelium and vascular smooth muscle cells. The renin-angiotensin system plays a crucial role in the maintenance of normal blood pressure. This function is mediated via the peptide hormone angiotensin II (ANG II), which maintains normal blood volume by regulating Na+ excretion. However, elevation of ANG II above normal levels increases O2•- production, promotes oxidative stress and endothelial dysfunction, and plays a major role in multiple disease conditions. Elevated dietary salt intake also leads to oxidant stress and endothelial dysfunction, but these occur in the face of salt-induced ANG II suppression and reduced levels of circulating ANG II. While the effects of abnormally high levels of ANG II have been extensively studied, far less is known regarding the mechanisms of oxidant stress and endothelial dysfunction occurring in response to chronic exposure to abnormally low levels of ANG II. The current article focuses on the mechanisms and consequences of this less well understood relationship among salt, superoxide, and endothelial function.

Interleukin 22 Promotes Blood Pressure Elevation and Endothelial Dysfunction in Angiotensin II–Treated Mice

“…Accumulating evidence has demonstrated that endothelial dysfunction promotes BP elevation and serves as a bridge between angiotensin II and hypertension . In the present study, we investigated whether IL‐22 plays a role in regulating endothelial function.…”

“…Accumulating evidence has demonstrated that endothelial dysfunction promotes BP elevation and serves as a bridge between angiotensin II and hypertension. 18,[41][42][43] In the present study, we investigated whether IL-22 plays a role in regulating endothelial function. The results showed that rIL-22 further promoted the effect of angiotensin II on endotheliumdependent and -independent relaxation responses, whereas anti-IL-22 mAb reversed the effect of angiotensin II.…”

Angiotensin-(1-7) Selectively Induces Relaxation and Modulates Endothelium-Dependent Dilation in Mesenteric Arteries of Salt-Fed Rats

“…These findings are especially relevant in light of recent studies showing that HS diet leads to endothelial dysfunction in healthy normotensive male [58] and female [59] humans. In this regard, the results of the present study suggest novel therapeutic targets including not only the mas receptor but also other components of the renin-angiotensin system to treat diseases associated with salt-induced endothelial dysfunction, chronically low angiotensin II levels, and vascular oxidant stress [60]. …”

Introductory Chapter: Microcirculation in Health and Disease

“…Contrary to the common accepted knowledge, they propose that sufficient levels of Ang actually are essential for normal vascular function, as confirmed in the studies which have demonstrated that a decrease in the circulating levels of Ang lead to impaired microvascular endothelial function [28]. As for Ang, Kolka additionally exposes its effect on blood vessel permeability which indirectly also affects the tissue metabolism [29].…”