Oxidative Stress in Arterial Hypertension

Abstract

Increased vascular reactive oxygen species production, especially superoxide anion, contributes significantly in the functional and structural alterations present in hypertension. An enhanced superoxide production causes a diminished NO bioavailability by an oxidative reaction that inactivates NO. Exaggerated superoxide levels and a low NO bioavailability lead to endothelial dysfunction and hypertrophy of vascular cells. It has been shown that the enzyme NAD(P)H oxidase plays a major role as the most important source of superoxide anion in vascular cells. Several experimental observations have shown an enhanced superoxide generation as a result of the activation of vascular NAD(P)H oxidase in hypertension. Although this enzyme responds to stimuli such as vasoactive factors, growth factors, and cytokines, some recent data suggest the existence of a genetic background modulating the expression of its different components. New polymorphisms have been identified in the promoter of the p22 phox gene, an essential subunit of NAD(P)H oxidase, influencing the activity of this enzyme. Genetic investigations of these polymorphisms will provide novel markers for determination of genetic susceptibility to oxidative stress in hypertension.

Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases

“…Persons with hypertension are at an increased risk for stroke, heart disease, kidney failure, and premature mortality. Free radical induced oxidative stress in part contributes to endothelial dysfunction and development of hypertension [169]. Increased ROS generation eliminates NO • by forming ONOO -, thus reducing NO • bioavailability which leads to decreased endothelium-dependent vasodilation resulting in hypertension [170].…”

Mechanisms of H2O2-induced oxidative stress in endothelial cells

“…Endothelial cell dysfunction is often associated with hypertension, due to elevated levels of shear stress. Higher levels of shear stress have been shown to damage the endothelium resulting in increased ROS formation, including O 2 ·- (Zalba et al 2001). …”

“…The reduction in nitric oxide availability is tied to increased O 2 ·-levels, mainly contributed by NADPH oxidase in smooth muscle cells, resulting in NO intereaction with O 2 ·-and the formation of peroxynitrite (ONOO -, (Landmesser et al 2002;Rathaus et al 2002). Loss of the NO-O 2 ·-balance results in cellular damage, contributing to hypertension and the loss of endothelial cell control of vessel dilation (Zalba et al 2001). Angiotensin II also stimulates NADPH oxidase formation of O 2 ·-, resulting in dysfunctional endothelial cells as discussed above (Hanna et al 2002;Landmesser et al 2002;Rocic et al 2003).…”

The effect of short-term canola oil ingestion on oxidative stress in the vasculature of stroke-prone spontaneously hypertensive rats

“…In hypertensive patients, vascular smooth muscle cells (VSMCs) from resistance arteries have increased ROS generation, and this increase is linked to NADPH oxidase [16]. Evidence has shown that in SHR and SHRSP rats there was an enhanced production of superoxide (·O 2 ˉ) derived from NADPH oxidase, and this was associated with the upregulation of p22 phox mRNA expression in the aorta [14,17]. Furthermore, NOX2 mRNA expression in the aorta was found to be greater in SHR compared to the normotensive WKY rats [18].…”