Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress.
Accumulating evidence suggests that oxidant stress alters many functions of the endothelium, including modulation of vasomotor tone, and as the role of these various enzyme sources of ROS become clear, it will perhaps be possible to use more specific therapies to prevent their production and ultimately correct endothelial dysfunction.
Role of the T cell in the genesis of angiotensin II–induced hypertension and vascular dysfunction
A previously undefined role for T cells in the genesis of hypertension is identified and a role of inflammation in the basis of this prevalent disease isSupporting a novel therapeutic target for the treatment of high blood pressure.
Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension.
Evidence is obtained that hypertension produces a cascade involving production of ROSs from the NADPH oxidase leading to oxidation of tetrahydrobiopterin and uncoupling of endothelial NO synthase (eNOS), which decreases NO production and increases ROS production from eNOS.
Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone.
Forms of hypertension associated with elevated circulating levels of angiotensin II may have unique vascular effects not shared by other forms of hypertension because they increase vascular smooth muscle .O2- production via NADH/NADPH oxidase activation.
Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability.
- S. Rajagopalan, X. Meng, S. Ramasamy, D. Harrison, Z. Galis
- BiologyJournal of Clinical Investigation
- 1 December 1996
It is shown that in vivo generated macrophage foam cells produce superoxide, nitric oxide, and hydrogen peroxide after isolation from hypercholesterolemic rabbits and reactive oxygen species can modulate matrix degradation in areas of high oxidant stress and could therefore contribute to instability of atherosclerotic plaques.
Interactions of Peroxynitrite, Tetrahydrobiopterin, Ascorbic Acid, and Thiols
- N. Kuzkaya, N. Weissmann, D. Harrison, S. Dikalov
- ChemistryJournal of Biological Chemistry
- 20 June 2003
It is confirmed that ONOO– uncouples eNOS by oxidation of tetrahydrobiopterin and that ascorbate does not fully protect BH4 from oxidation but recycles its radical, and that the BH 4 reaction rate constant exceeds those of thiols or asCorbate.
The vascular NAD(P)H oxidases as therapeutic targets in cardiovascular diseases.
Hypercholesterolemia increases endothelial superoxide anion production.
Increased endothelial O2- production in HV may inactivate endothelium-derived nitric oxide and provide a source for other oxygen radicals, contributing to the early atherosclerotic process.
Therapeutic targeting of mitochondrial superoxide in hypertension
It is possible that commonly employed antioxidants have proven ineffective in clinical trials because they are not adequately delivered to the subcellular sites of O2• production.
Endothelial Regulation of Vasomotion in ApoE-Deficient Mice: Implications for Interactions Between Peroxynitrite and Tetrahydrobiopterin
Reactive oxygen species may alter endothelium-dependent vascular relaxation not only by the interaction of O2·− with NO· but also through interactions between peroxynitrite and tetrahydrobiopterin.