Angiotensin II Induces Oxidative Stress and Endothelial Dysfunction in Mouse Ophthalmic Arteries via Involvement of AT1 Receptors and NOX2
Michael Birk,
Ewa Baum,
Jenia Kouchek Zadeh,
Caroline Manicam,
Norbert Pfeiffer,
Andreas Patzak,
Johanna Helmstädter,
Sebastian Steven,
Marin Kuntic,
Andreas Daiber,
Adrian Gericke
Affiliations
Michael Birk
Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany
Ewa Baum
Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany
Jenia Kouchek Zadeh
Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany
Caroline Manicam
Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany
Norbert Pfeiffer
Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany
Andreas Patzak
Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany
Johanna Helmstädter
Department of Cardiology, Cardiology I-Laboratory of Molecular Cardiology, University Medical Center, Johannes Gutenberg University, Building 605, Langenbeckstr. 1, 55131 Mainz, Germany
Sebastian Steven
Department of Cardiology, Cardiology I-Laboratory of Molecular Cardiology, University Medical Center, Johannes Gutenberg University, Building 605, Langenbeckstr. 1, 55131 Mainz, Germany
Marin Kuntic
Department of Cardiology, Cardiology I-Laboratory of Molecular Cardiology, University Medical Center, Johannes Gutenberg University, Building 605, Langenbeckstr. 1, 55131 Mainz, Germany
Andreas Daiber
Department of Cardiology, Cardiology I-Laboratory of Molecular Cardiology, University Medical Center, Johannes Gutenberg University, Building 605, Langenbeckstr. 1, 55131 Mainz, Germany
Adrian Gericke
Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany
Angiotensin II (Ang II) has been implicated in the pathophysiology of various age-dependent ocular diseases. The purpose of this study was to test the hypothesis that Ang II induces endothelial dysfunction in mouse ophthalmic arteries and to identify the underlying mechanisms. Ophthalmic arteries were exposed to Ang II in vivo and in vitro to determine vascular function by video microscopy. Moreover, the formation of reactive oxygen species (ROS) was quantified and the expression of prooxidant redox genes and proteins was determined. The endothelium-dependent artery responses were blunted after both in vivo and in vitro exposure to Ang II. The Ang II type 1 receptor (AT1R) blocker, candesartan, and the ROS scavenger, Tiron, prevented Ang II-induced endothelial dysfunction. ROS levels and NOX2 expression were increased following Ang II incubation. Remarkably, Ang II failed to induce endothelial dysfunction in ophthalmic arteries from NOX2-deficient mice. Following Ang II incubation, endothelium-dependent vasodilation was mainly mediated by cytochrome P450 oxygenase (CYP450) metabolites, while the contribution of nitric oxide synthase (NOS) and 12/15-lipoxygenase (12/15-LOX) pathways became negligible. These findings provide evidence that Ang II induces endothelial dysfunction in mouse ophthalmic arteries via AT1R activation and NOX2-dependent ROS formation. From a clinical point of view, the blockade of AT1R signaling and/or NOX2 may be helpful to retain or restore endothelial function in ocular blood vessels in certain ocular diseases.