Enhanced Oxidative Stress and Impaired Thioredoxin Expression in Spontaneously Hypertensive Rats

Tanito, Masaki; Nakamura, Hajime; Kwon, Yong-Won; Teratani, Akie; Masutani, Hiroshi; Shioji, Kosei; Kishimoto, Chiharu; Ohira, Akihiro; Horie, Ryoichi; Yodoi, Junji

doi:10.1089/152308604771978381

Cited by 149 publications

(99 citation statements)

References 40 publications

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“…The TRX/GRX enzyme systems are especially important in protecting against ischemia/reperfusion injury after myocardial infarction, atherosclerotic plaque rupture, left ventricular hypertrophy in congestive heart failure, and kidney oxidative stress. In SHRs and SHRSP rats, TRX levels were lower in kidneys by both immunohistochemistry/Western blots and real time PCR, when compared with those in normal WKY rats (319). Of note, whereas the roles of TRX/GRX systems are better understood in the cardiovascular disease, their role in the kidney is just emerging.…”

Section: Nistala Et Al 2054mentioning

confidence: 93%

Redox Control of Renal Function and Hypertension

Nistala

Whaley‐Connell

Sowers

2008

Antioxidants & Redox Signaling

138

123

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Section: Nistala Et Al 2054mentioning

confidence: 93%

Redox Control of Renal Function and Hypertension

Nistala

Whaley‐Connell

Sowers

2008

Antioxidants & Redox Signaling

138

123

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“…The effects of ROS are mediated through redoxsensitive regulation of multiple signaling molecules and second messengers. [5][6][7] Several studies have demonstrated excessive amounts of ROS in essential hypertensive patients and various animal models of hypertension; [8][9][10][11][12] these patients and experimental animals have a diminished antioxidant status, 13 which contributes to the accumulating evidence that increased vascular oxidative stress could be involved in the pathogenesis of essential hypertension. 2,3,14 Recently, a strong association between blood pressure and some oxidative stress-related parameters was demonstrated.…”

Section: Vascular Oxidative Stress and Hypertensionmentioning

confidence: 99%

“…78,79 Recent studies have demonstrated the importance of the thioredoxin system in the maintenance of a reduced redox state and in the pathophysiology of hypertension. 80 It has been reported that Oxidative stress in hypertension R Rodrigo et al impaired thioredoxin expression in spontaneously hypertensive rats 81 and in endothelial cells negatively regulates ROS production in VSMC through thioredoxin upregulation. 82 Thus, thioredoxin could be an important therapeutic target for the prevention and treatment of oxidative stress and hypertension.…”

Section: Endogenous Antioxidantsmentioning

confidence: 99%

The role of oxidative stress in the pathophysiology of hypertension

2011

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Hypertension is considered to be the most important risk factor in the development of cardiovascular disease. An increasing body of evidence suggests that oxidative stress, which results in an excessive generation of reactive oxygen species (ROS), has a key role in the pathogenesis of hypertension. The modulation of the vasomotor system involves ROS as mediators of vasoconstriction induced by angiotensin II, endothelin-1 and urotensin-II, among others. The bioavailability of nitric oxide (NO), which is a major vasodilator, is highly dependent on the redox status. Under physiological conditions, low concentrations of intracellular ROS have an important role in the normal redox signaling maintaining vascular function and integrity. However, under pathophysiological conditions, increased levels of ROS contribute to vascular dysfunction and remodeling through oxidative damage. In human hypertension, an increase in the production of superoxide anions and hydrogen peroxide, a decrease in NO synthesis and a reduction in antioxidant bioavailability have been observed. In turn, antioxidants are reducing agents that can neutralize these oxidative and otherwise damaging biomolecules. The use of antioxidant vitamins, such as vitamins C and E, has gained considerable interest as protecting agents against vascular endothelial damage. Available data support the role of these vitamins as effective antioxidants that can counteract ROS effects. This review discusses the mechanisms involved in ROS generation, the role of oxidative stress in the pathogenesis of vascular damage in hypertension, and the possible therapeutic strategies that could prevent or treat this disorder. Hypertension Research (2011) 34, 431-440; doi:10.1038/hr.2010.264; published online 13 January 2011Keywords: antioxidants; endothelial dysfunction; oxidative stress INTRODUCTION Hypertension is considered the most important risk factor for the occurrence of cardiovascular disease. 1 Oxidative stress has gained attention as one of the fundamental mechanisms responsible for the development of hypertension. Reactive oxygen species (ROS) have an important role in the homeostasis of the vascular wall; hence, they could be part of the mechanism that leads to hypertension. 2-4 Thus, increased ROS production, reduced nitric oxide (NO) levels and reduced antioxidant bioavailability were demonstrated in experimental and human hypertension. Vascular superoxide is primarily derived from nicotinamide adenine dineucleotide phosphate (NADPH) oxidase when stimulated by hormones, such as angiotensin II (AT-II), endothelin-1 (ET-1) and urotensin II. In addition, increased ROS production may be generated by mechanical stimuli on the vascular wall, which increase with hypertension. ROS-induced vasoconstriction results from increased intracellular calcium concentration, thereby contributing to the pathogenesis of hypertension. 2 Vasomotor tone is dependent on a delicate balance between vasoconstrictor and vasodilator forces that result from the interaction between the components of...

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“…Although very little is known about the relationship between TRX and Ang II, there is evidence that the TRX system is modulated by the renin angiotensin system, since ACE inhibition improves severity of myocarditis via redox regulation mechanisms involving TRX. In addition, in SHR, a model of Ang II-dependent hypertension, vascular TRX expression is impaired (60).…”

Section: Processes Whereby Ros Influence Signaling Moleculesmentioning

confidence: 99%

Reactive oxygen species and angiotensin II signaling in vascular cells: implications in cardiovascular disease

Touyz

2004

Braz J Med Biol Res

273

152

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Diseases such as hypertension, atherosclerosis, hyperlipidemia, and diabetes are associated with vascular functional and structural changes including endothelial dysfunction, altered contractility and vascular remodeling. Cellular events underlying these processes involve changes in vascular smooth muscle cell (VSMC) growth, apoptosis/anoikis, cell migration, inflammation, and fibrosis. Many factors influence cellular changes, of which angiotensin II (Ang II) appears to be amongst the most important. The physiological and pathophysiological actions of Ang II are mediated primarily via the Ang II type 1 receptor. Growing evidence indicates that Ang II induces its pleiotropic vascular effects through NADPH-driven generation of reactive oxygen species (ROS). ROS function as important intracellular and intercellular second messengers to modulate many downstream signaling molecules, such as protein tyrosine phosphatases, protein tyrosine kinases, transcription factors, mitogen-activated protein kinases, and ion channels. Induction of these signaling cascades leads to VSMC growth and migration, regulation of endothelial function, expression of pro-inflammatory mediators, and modification of extracellular matrix. In addition, ROS increase intracellular free Ca 2+ concentration ([Ca 2+ ] i ), a major determinant of vascular reactivity. ROS influence signaling molecules by altering the intracellular redox state and by oxidative modification of proteins. In physiological conditions, these events play an important role in maintaining vascular function and integrity. Under pathological conditions ROS contribute to vascular dysfunction and remodeling through oxidative damage. The present review focuses on the biology of ROS in Ang II signaling in vascular cells and discusses how oxidative stress contributes to vascular damage in cardiovascular disease.

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Enhanced Oxidative Stress and Impaired Thioredoxin Expression in Spontaneously Hypertensive Rats

Cited by 149 publications

References 40 publications

Redox Control of Renal Function and Hypertension

Redox Control of Renal Function and Hypertension

The role of oxidative stress in the pathophysiology of hypertension

Reactive oxygen species and angiotensin II signaling in vascular cells: implications in cardiovascular disease

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