Angiotensin II–Dependent Superoxide

Welch, William J.

doi:10.1161/hypertensionaha.107.090472

Cited by 94 publications

(28 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…8,9 However, there have been conflicting results regarding the role of AngII-generated ROS actions on various vascular consequences, including hypertension, hypertrophy and inflammation. 1,2 …”

Section: Introductionmentioning

confidence: 99%

TLR4 is a critical regulator of angiotensin II-induced vascular remodeling: the roles of extracellular SOD and NADPH oxidase

et al. 2015

View full text Add to dashboard Cite

Toll-like receptor 4 (TLR4) and angiotensin II (AngII) induce vascular remodeling through the production of reactive oxygen species (ROS). AngII has also been shown to increase antioxidant enzyme extracellular superoxide dismutase (ecSOD). However, the roles of TLR4 in Ang II-induced ROS production, vascular remodeling and hypertension remain unknown. Mice lacking TLR4 function showed significant inhibition of vascular remodeling in response to chronic AngII infusion, with no impact on blood pressure. The increases in ROS level and NADPH oxidase activity in response to AngII infusion were markedly blunted in TLR4-deficient mice. Similar effects were observed in wild-type (WT) mice treated with a sub-depressor dose of the AT1 receptor antagonist irbesartan, which had no effects on TLR4-deficient mice. Intriguingly, the AngII infusion-induced increases in ecSOD activity and expression were rather enhanced in TLR4-deficient mice compared with WT mice, whereas the expression of the proinflammatory chemokine MCP-1 was decreased. Importantly, AngII-induced vascular remodeling was positively correlated with NADPH oxidase activity, ROS levels and MCP-1 expression levels. Notably, chronic norepinephrine infusion, which elevates blood pressure without increasing ROS production, did not induce significant vascular remodeling in WT mice. Taken together, these findings suggest that ROS elevation is required for accelerating vascular remodeling but not for hypertensive effects in this model. We demonstrated that TLR4 plays a pivotal role in regulating AngII-induced vascular ROS levels by inhibiting the expression and activity of the antioxidant enzyme ecSOD, as well as by activating NADPH oxidase, which enhances inflammation to facilitate the progression of vascular remodeling.

show abstract

Section: Introductionmentioning

confidence: 99%

TLR4 is a critical regulator of angiotensin II-induced vascular remodeling: the roles of extracellular SOD and NADPH oxidase

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Regulation of NADPH oxidase activity can be achieved by modulation of angiotesin II (Ang II) receptor 1 (AT1R). Several AT1R antagonists have been shown to reduce reactive oxidative stress in human and animals [19,20]. Collectively, the oxidative balance regulates the degree of tone or vasodilatation and hence the stretch in the vessel wall.…”

Section: Introductionmentioning

confidence: 99%

Role of shear stress and stretch in vascular mechanobiology

Kassab

2011

J. R. Soc. Interface.

272

198

View full text Add to dashboard Cite

Blood vessels are under constant mechanical loading from blood pressure and flow which cause internal stresses (endothelial shear stress and circumferential wall stress, respectively). The mechanical forces not only cause morphological changes of endothelium and blood vessel wall, but also trigger biochemical and biological events. There is considerable evidence that physiologic stresses and strains (stretch) exert vasoprotective roles via nitric oxide and provide a homeostatic oxidative balance. A perturbation of tissue stresses and strains can disturb biochemical homeostasis and lead to vascular remodelling and possible dysfunction (e.g. altered vasorelaxation, tone, stiffness, etc.). These distinct biological endpoints are caused by some common biochemical pathways. The focus of this brief review is to point out some possible commonalities in the molecular pathways in response to endothelial shear stress and circumferential wall stretch.

show abstract

“…In contrast to the neutrophil NADPH oxidase, the enzyme complex in nonphagocytic cells continuously forms low levels of superoxide intracellularly and can be further activated by agonists such as angiotensin II (11). Angiotensin II activates NADPH oxidase either by up-regulating subunits, like Nox1, p22phox, p47phox, and p67phox (3,12), or by facilitating the assembly of the subunits (13,14). Nox4 is unique because it seems to operate constitutively, being regulated at the mRNA level (15,16).…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II Induces DNA Damage in the Kidney

et al. 2008

View full text Add to dashboard Cite

Increased activity of the renin angiotensin system with enhanced levels of angiotensin II leads to oxidative stress with endothelial dysfunction, hypertension, and atherosclerosis. Epidemiologic studies revealed a higher cancer mortality and an increased kidney cancer incidence in hypertensive patients. Because elevated angiotensin II levels might contribute to carcinogenesis, we tested whether angiotensin II induces DNA damage in the kidney. In isolated perfused mouse kidneys, as little as 1 nmol/L angiotensin II caused a significant increase in DNA strand breaks, measured with the comet assay. This damage was independent of the hemodynamic effect of angiotensin II and mediated by the angiotensin II type 1 receptor. Angiotensin II also caused double-strand breaks in the cells of the isolated perfused kidney, detected with an antibody against the double-strand break marker ;-H2AX. Studies in cell culture allowed further characterization of the DNA damage induced by angiotensin II. Single-and double-strand breaks, abasic sites, and 7,8-dihydro-8-oxoguanine, all types of oxidative DNA lesions, were detected in angiotensin II-treated renal cells. The majority of detected strand breaks was repaired within 1 hour, but double-strand breaks increased and persisted for at least 24 hours. [Cancer Res 2008;68(22):9239-46]

show abstract

Angiotensin II–Dependent Superoxide

Cited by 94 publications

References 51 publications

TLR4 is a critical regulator of angiotensin II-induced vascular remodeling: the roles of extracellular SOD and NADPH oxidase

TLR4 is a critical regulator of angiotensin II-induced vascular remodeling: the roles of extracellular SOD and NADPH oxidase

Role of shear stress and stretch in vascular mechanobiology

Angiotensin II Induces DNA Damage in the Kidney

Contact Info

Product

Resources

About