Angiotensin II Induces Oxidative Stress and Endothelial Dysfunction in Mouse Ophthalmic Arteries via Involvement of AT1 Receptors and NOX2

Birk, Michael; Baum, Ewa; Zadeh, Jenia Kouchek; Manicam, Caroline; Pfeiffer, Norbert; Patzak, Andreas; Helmstädter, Johanna; Steven, Sebastian; Kuntic, Marin; Daiber, Andreas; Gericke, Adrian

doi:10.3390/antiox10081238

Cited by 28 publications

(20 citation statements)

References 68 publications

(93 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Excessive ROS levels induce endothelial dysfunction via multiple mechanisms, such as uncoupling of eNOS from generation of nitric oxide or by reducing connexin and/or calcium-activated potassium channel expression resulting in impaired endothelium-derived hyperpolarizing factor (EDHF)-dependent responses [ 2 , 46 , 47 ]. In the mouse ophthalmic artery, where eNOS contributes only partially to endothelium-dependent vasodilation [ 48 , 49 , 50 ], excessive ROS formation was shown to affect various endothelial vasodilatory signaling pathways [ 51 ]. However, in retinal arterioles eNOS is the major mediator of endothelial vasodilatory responses, suggesting that eNOS uncoupling is the main mechanism via which ROS induce endothelial dysfunction [ 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Resveratrol on Vascular Function in Retinal Ischemia-Reperfusion Injury

et al. 2023

Self Cite

View full text Add to dashboard Cite

Ischemia-reperfusion (I/R) events are involved in the development of various ocular pathologies, e.g., retinal artery or vein occlusion. We tested the hypothesis that resveratrol is protective against I/R injury in the murine retina. Intraocular pressure (IOP) was elevated in anaesthetized mice to 110 mm Hg for 45 min via a micropipette placed in the anterior chamber to induce ocular ischemia. In the fellow eye, which served as control, IOP was kept at a physiological level. One group received resveratrol (30 mg/kg/day p.o. once daily) starting one day before the I/R event, whereas the other group of mice received vehicle solution only. On day eight after the I/R event, mice were sacrificed and retinal wholemounts were prepared and immuno-stained using a Brn3a antibody to quantify retinal ganglion cells. Reactivity of retinal arterioles was measured in retinal vascular preparations using video microscopy. Reactive oxygen species (ROS) and nitrogen species (RNS) were quantified in ocular cryosections by dihydroethidium and anti-3-nitrotyrosine staining, respectively. Moreover, hypoxic, redox and nitric oxide synthase gene expression was quantified in retinal explants by PCR. I/R significantly diminished retinal ganglion cell number in vehicle-treated mice. Conversely, only a negligible reduction in retinal ganglion cell number was observed in resveratrol-treated mice following I/R. Endothelial function and autoregulation were markedly reduced, which was accompanied by increased ROS and RNS in retinal blood vessels of vehicle-exposed mice following I/R, whereas resveratrol preserved vascular endothelial function and autoregulation and blunted ROS and RNS formation. Moreover, resveratrol reduced I/R-induced mRNA expression for the prooxidant enzyme, nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2). Our data provide evidence that resveratrol protects from I/R-induced retinal ganglion cell loss and endothelial dysfunction in the murine retina by reducing nitro-oxidative stress possibly via suppression of NOX2 upregulation.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of Resveratrol on Vascular Function in Retinal Ischemia-Reperfusion Injury

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…Many others concluded the same results, Chen et al, 2020; Cook and Ausiello, 2021 found that Ang II levels increased with advanced age and hypertension due to ACE2 deficiency, whereas this enzyme was responsible for the conversion of Ang II to Ang 1-7, which led to a decrease in Ang 1-7. Also, the Ang 1-7 age-related deficiency is associated with a concomitant enhanced Ang II production, moreover, Ang II increased in aging and hypertensive mice related to oxidative stress, endothelial dysfunction, and inflammation (Jia et al, 2019; Birk et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

The Activity of Angiotensin-Converting Enzyme 2 and Other Components of the Renin-Angiotensin System (Raas) During Progressive Age in Hypertensive Men

Khalifa¹,

Hasan²

2023

PTQ

View full text Add to dashboard Cite

Background: ACE2 and renin-angiotensin-aldosterone system (RAAS) are complex physiological systems that contribute to blood pressure control, whereas the activity and responsiveness of the ACE2 and RAAS be changed due to advanced age and hypertension. Aim: This study is to investigate the ACE2, Renin, Ang I, Ang II, and aldosterone levels in various ages of hypertensive men in order to provide insights into the effect of aging and high blood pressure on some body organs. Methods: It was compared ACE2, Renin, Ang I, Ang II, and aldosterone levels across 80 hypertensive men with ages between 30 years - 69 years. The persons were divided into four groups (20 men/group) according to their ages. The first group was 30-39 years, the second group was 40-49 years, the third group was 50-59 years, and the fourth group was 60-69. It used a one-way Analysis of Variance (ANOVA), followed by Duncan s test for the groups. Results: It was observed that the concentration of ACE2 decreased significantly in different groups with advanced age (p ≤ 0.01), except in the fourth sample group vs. the third group. The renin was reduced considerably in other groups with aging (p ≤ 0.01), except in the second sample group vs. the first group. The peptides Angiotensin I (Ang I) and Angiotensin II (Ang II) had opposite growth directions, decreasing and increasing, respectively, it was statistically significant (p ≤ 0.01). Also, aldosterone increased significantly in different groups with advanced age (p ≤ 0.01), not including the fourth group vs. the third group). Discussion: The physiological impact of these results is discussed according to the effects of hypertension and advanced age on all the studied parameters, particularly ACE2 deficiency and high levels of Ang II, pointed out an apparent dysfunction in blood pressure regulation during advanced age. Conclusions: ACE2 deficiency may be mediated by a series of dysfunctional events caused by the present changes in RAAS and other parameters in response to hypertension and advanced ages. Low renin levels and other following changes might cause an imbalance of Ang I and Ang II ratios. In addition, high levels of Ang II might reflect the unfavorable and negative changes that contributed to the disruption of many organs and systems during hypertension and advanced age.

show abstract

“…It was documented that angiotensin II (Ang II) was implicated in the pathology of AMD. It was shown that Ang II can mediate various pathological processes in ocular blood vessels such as proliferation and migration of smooth muscle cells and pericytes, increase of VEGF expression and potentiation of VEGF-dependent angiogenic activity [106,107]. Receptors for AngII have been identified in retinal and optic nerve blood vessels.…”

Section: Other Mechanisms Involved In the Development Of Neovascular Amdmentioning

confidence: 99%

The Role of Oxidative Stress in the Onset and Development of Age-Related Macular Degeneration

Čolak¹,

Zoric²,

Mirkovic³

et al. 2023

Importance of Oxidative Stress and Antioxidant System in Health and Disease

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is a complex, degenerative and progressive chronic disease that leads to severe visual loss. The prevalence of early AMD accounts for 18% in the population between 65 and 74 years of age and even 30% in subjects older than 74 years. The articles published in the last decade point out to a significant role of oxidative stress in the onset and development of age-related macular degeneration. Generally, reactive oxygen species (ROS) are produced in the eye during light absorption and physiological metabolic processes. The level of oxidative stress is kept under control by the action of antioxidants and reparative enzymes. Excessive synthesis of ROS leads to increased oxidative modification of lipids, proteins and DNA, causing oxidative damage of cytoplasmic and nuclear cell elements and changes of the extracellular matrix. The accumulation of oxidatively modified compounds in drusen deposits will initiate the onset and development of AMD. The objective of this review was to highlight the mechanisms of oxidative stress in order to elucidate their significance and association with the pathogenesis of AMD.

show abstract

Angiotensin II Induces Oxidative Stress and Endothelial Dysfunction in Mouse Ophthalmic Arteries via Involvement of AT1 Receptors and NOX2

Cited by 28 publications

References 68 publications

Effects of Resveratrol on Vascular Function in Retinal Ischemia-Reperfusion Injury

Effects of Resveratrol on Vascular Function in Retinal Ischemia-Reperfusion Injury

The Activity of Angiotensin-Converting Enzyme 2 and Other Components of the Renin-Angiotensin System (Raas) During Progressive Age in Hypertensive Men

The Role of Oxidative Stress in the Onset and Development of Age-Related Macular Degeneration

Contact Info

Product

Resources

About