Induction of Oxidative Stress by Glutathione Depletion Causes Severe Hypertension in Normal Rats

Vaziri, Nosratola D.; Wang, Xiu Q.; Oveisi, Fariba; Rad, Behdad

doi:10.1161/01.hyp.36.1.142

Cited by 371 publications

(288 citation statements)

References 43 publications

(43 reference statements)

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“…This is supported by the finding that treatment of BSO rats with tempol decreased oxidative stress, restored the NO-mediated relaxation and signaling, corrected eNOS expression, and normalized BP. These studies are in agreement with Vaziri et al 37 showing that BSO caused oxidative stress and increased BP, and these changes were reversed by antioxidant supplementation.…”

Section: Oxidative Stress Vascular Function and Bpsupporting

confidence: 92%

Mechanisms of Oxidative Stress-Induced Increase in Salt Sensitivity and Development of Hypertension in Sprague-Dawley Rats

et al. 2007

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Abstract-High salt intake produces vascular changes that contribute to the development of hypertension in salt-sensitive individuals. Because reactive oxygen species play a role in the pathogenesis of cardiovascular diseases, we investigated whether oxidative stress contributes to salt-sensitive hypertension. Sprague-Dawley rats were divided in different groups and received tap water (vehicle), 30 mmol/L of L-buthionine sulfoximine ([BSO] an oxidant), high salt ([HS] 1% NaCl), and BSO plus HS without and with antioxidant tempol (1 mmol/L) in drinking water for 12 days. Compared with vehicle, BSO treatment caused oxidative stress and mild increase in blood pressure. Thoracic aortic rings from BSO-treated rats exhibited decreased response to endothelium-independent vasorelaxants. In HS-treated rats, the response to vasoactive agents, as well as blood pressure, was unaffected. Concomitant treatment of rats with BSO and HS produced a marked increase in blood pressure and a decreased response to both endothelium-dependent and endothelium-independent vasorelaxants with an increase in EC 50 . Incubation of aortic tissue from BSO-treated rats with sodium nitroprusside showed decreased cGMP accumulation, whereas HS rats had decreased basal NO synthase activity. Tempol decreased oxidative stress, normalized blood pressure, and restored NO signaling and responses to vasoactive compounds in BSO and BSO plus HS rats. We conclude that BSO increases oxidative stress and reduces NO signaling, whereas HS reduces NO levels by decreasing the NO synthase activity. These phenomena collectively result in reduced responsiveness to both endothelium -dependent and endothelium-independent vasorelaxants and may contribute to salt-sensitive hypertension. Key Words: acetylcholine Ⅲ hypertension Ⅲ oxidative stress Ⅲ salt sensitivity Ⅲ tempol E ndothelial cells modulate the reactivity of the underlying vascular smooth muscle cells by releasing endotheliumderived relaxing factors. 1,2 Previous studies have demonstrated that elevated dietary salt intake leads to an impaired relaxation of blood vessels to endothelium-dependent relaxations induced by a variety of vasodilator agents. 3-9 A possible contributor to impaired vascular relaxation to dilator stimuli in animals on a high-salt diet is an impaired function of the endothelium. 3-9 Impaired endothelium-dependent dilation in vessels of animals on a high-salt diet could occur either because the acetylcholine (Ach)-mediated production of NO by the endothelium is impaired or because of the failure of NO to cause vasodilation. [3][4][5][6][7][8][9] NO is a major regulator of vascular tone in humans. 10 Decreased production or bioavailability, or decreased vascular response to NO, has been implicated in the pathogenesis of human hypertension. 11,12 An increase in blood pressure (BP) in response to dietary sodium (salt sensitivity) is a well-documented phenomenon in humans and is considered to be an important factor in the pathogenesis of hypertension. 4 In animal models of salt-sensitive hypertens...

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Section: Oxidative Stress Vascular Function and Bpsupporting

confidence: 92%

Mechanisms of Oxidative Stress-Induced Increase in Salt Sensitivity and Development of Hypertension in Sprague-Dawley Rats

et al. 2007

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“…24 -26 Moreover, the induction of chronic oxidative stress by glutathione depletion has been shown to cause severe hypertension in normotensive rats. 27 There is also some evidence for similar mechanisms in human endothelial dysfunction and essential hypertension. 28,29 Although an alternative explanation may be that changes in the levels of Gstm2 expression between the strains are secondary to blood pressure differences already present in 15-week-old rats.…”

Section: Discussionmentioning

confidence: 99%

Microarray Analysis of Rat Chromosome 2 Congenic Strains

et al. 2003

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Abstract-Human essential hypertension is a complex polygenic trait with underlying genetic components that remain unknown. The stroke-prone spontaneously hypertensive rat (SHRSP) is a model of human essential hypertension, and a number of reproducible blood pressure regulation quantitative trait loci have been found to map to rat chromosome 2. The SP.WKYGla2c* congenic strain was produced by introgressing a region of rat chromosome 2 from the normotensive Wistar Kyoto (WKY) strain into the genetic background of the SHRSP.

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“…Hypertension increases endothelial oxidative stress and inflammation and leads to worse stroke outcomes and higher mortality [210][211][212][213][214][215][216][217][218][219][220]. Studies investigating the underlying pathophysiology of hypertension indicates the involvement of neuroimmune interactions.…”

Section: Hypertensionmentioning

confidence: 99%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

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Historically, the brain has been considered an immune-privileged organ separated from the peripheral immune system by the blood-brain barrier. However, immune responses do occur in the brain in neurological conditions in which the integrity of the blood-brain barrier is compromised, exposing the brain to peripheral antigens and endogenous danger signals. While most of the associated pathological processes occur in the central nervous system, it is now clear that peripheral immune cells, especially mononuclear phagocytes, that infiltrate into the injury site play a key role in modulating the progression of primary brain injury development. As inflammation is a necessary and critical component for the subsequent injury resolution process, understanding the contribution of mononuclear phagocytes on the regulation of inflammatory responses may provide novel approaches for potential therapies. Furthermore, predisposed comorbid conditions at the time of stroke cause the alteration of stroke-induced immune and inflammatory responses and subsequently influence stroke outcome. In this review, we summarize a role for microglia and monocytes/macrophages in acute ischemic stroke in the context of normal and metabolically compromised conditions.

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Induction of Oxidative Stress by Glutathione Depletion Causes Severe Hypertension in Normal Rats

Cited by 371 publications

References 43 publications

Mechanisms of Oxidative Stress-Induced Increase in Salt Sensitivity and Development of Hypertension in Sprague-Dawley Rats

Mechanisms of Oxidative Stress-Induced Increase in Salt Sensitivity and Development of Hypertension in Sprague-Dawley Rats

Microarray Analysis of Rat Chromosome 2 Congenic Strains

Microglia and Monocyte-Derived Macrophages in Stroke

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