title: Oxidative stress and endothelial dysfunction in cerebrovascular disease.
abstract: Maintenance of vascular tone by the endothelium involves the production of endothelium-derived nitric oxide (NO). NO, produced from endothelial nitric oxide synthase diffuses to the underlying smooth muscle to stimulate soluble guanylate cyclase, resulting in increased cyclic GMP levels, and subsequent smooth muscle relaxation and blood vessel dilatation. Endothelial dysfunction, manifested as diminished NO bioavailability, is a common feature of a number of vascular-related diseases.. Oxidative stress can be defined as an imbalance between reactive oxygen species (ROS) production and/or impaired ROS metabolism that favours them being present in excess of physiological levels. Oxidative stress can negatively impact many cell types, including in the vasculature. There is now a wealth of evidence suggesting that oxidative stress is a major cause of endothelial dysfunction in the cerebral circulation. This review will summarize disease models in which both oxidative stress and endothelial dysfunction occur in the cerebral circulation, namely hypertension involving angiotensin II (Ang II), diabetes, subarachnoid hemorrhage, stroke and Alzheimer's disease. Molecular mechanisms by which oxidative stress occurs, (eg increased NADPH-oxidase activity) will also be discussed.
authors.affiliation: Vascular Biology and Immunopharmacology Group, Department of Pharmacology, Monash University, Wellington Rd, Clayton, Victoria 3800, Australia.
authors.forename: Sophocles
authors.initials: S
authors.lastname: Chrissobolis
authors.forename: Alyson A
authors.initials: AA
authors.lastname: Miller
authors.forename: Grant R
authors.initials: GR
authors.lastname: Drummond
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Kemp-Harper
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Sobey
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology; D000581:Amidohydrolases / Q000172:deficiency; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D008928:Mitochondria / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D015427:Reperfusion Injury / Q000503:physiopathology; D020521:Stroke / Q000503:physiopathology; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000172:deficiency
chemical_list: D000804:Angiotensin II; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases; D013482:Superoxide Dismutase; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D000581:Amidohydrolases; C059999:dimethylargininase