N-Acetylcysteine improves renal dysfunction, ameliorates kidney damage and decreases blood pressure in salt-sensitive hypertension

Tian, Niu; Rose, Rebecca; Jordan, Sharkeshia; Dwyer, Terry; Hughson, Michael D.; Manning, R. Davis

doi:10.1097/01.hjh.0000249705.42230.73

Cited by 43 publications

(41 citation statements)

References 35 publications

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“…The antioxidant N-acetylcysteine, which is a sulfhydryl group donor, improves renal dysfunction and decreases arterial pressure and renal injury in salt-sensitive hypertension. 145 The inhibition of oxidative stress in hypertensive states probably contributes to the therapeutic effects of N-acetylcysteine, which are likely mediated via a NO-dependent mechanism. 146 This protective mechanism is exerted by the prevention of BH 4 oxidation by the increased superoxide.…”

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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Section: Endogenous Antioxidantsmentioning

confidence: 99%

The role of oxidative stress in the pathophysiology of hypertension

2011

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“…Attenuated hypertension in young SHR [265] Prevented the development of glucocorticoidinduced hypertension [202] Prevented the development of adrenocorticotropic hormone-induced hypertension [266] Markedly reduced salt-sensitive hypertension [267] Prevented/ attenuated hypertension induced by nitric oxide synthesis inhibition [268] Failed to reduce blood pressure in adult SHR [265] Failed to attenuate glucorticoidinduced hypertension [202] Failed to reverse adrenocorticotropicinduced hypertension [266] Failed to prevent the development of hypertension induced by the blockade of nitric oxide synthesis [256] …”

Section: Nacmentioning

confidence: 99%

Lipid Peroxidation and Antioxidants in Arterial Hypertension

Sousa¹,

Afonso²,

Albino‐Teixeira³

et al. 2012

Lipid Peroxidation

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“…After 3 wk on the diets, catheters were implanted into the femoral artery and vein using isoflurane anesthesia (1%). After 4 days of recovery, a 10-day period of collection of arterial pressure, heart rate, and renal hemodynamics data began as has been done before by our group (22,43,45,46). GFR and effective renal plasma flow (ERPF) were determined in conscious rats on day 34, as has been done before by our group (21, 44).…”

mentioning

confidence: 99%

Interactions between oxidative stress and inflammation in salt-sensitive hypertension

Tian¹,

Moore²,

Braddy³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Tian N, Moore RS, Braddy S, Rose RA, Gu JW, Hughson MD, Manning RD Jr. Interactions between oxidative stress and inflammation in salt-sensitive hypertension. Am J Physiol Heart Circ Physiol 293: H3388-H3395, 2007. First published October 5, 2007; doi:10.1152/ajpheart.00981.2007.-The goal of this study was to test the hypothesis that increases in oxidative stress in Dahl S rats on a high-salt diet help to stimulate renal nuclear factor-B (NF-B), renal proinflammatory cytokines, and chemokines, thus contributing to hypertension, renal damage, and dysfunction. We specifically studied whether antioxidant treatment of Dahl S rats on high Na intake would decrease renal inflammation and thus attenuate the hypertensive and adverse renal responses. Sixty-four 7-to 8-wk-old Dahl S or R/Rapp strain rats were maintained for 5 wk on high Na (8%) or high Na ϩ vitamins C (1 g/l in drinking water) and E (5,000 IU/kg in food). Arterial and venous catheters were implanted at day 21. By day 35 in the high-Na S rats, antioxidant treatment significantly increased the renal reduced-to-oxidized glutathione ratio and decreased renal cortical H 2O2 and O2•Ϫ release and renal NF-B. Antioxidant treatment with vitamins C and E in high-Na S rats also decreased renal monocytes/macrophages in the glomeruli, cortex, and medulla, decreased tumor necrosis factor-␣ by 39%, and decreased monocyte chemoattractant protein-1 by 38%. Vitamin-treated, high-Na S rats also experienced decreases in arterial pressure, urinary protein excretion, renal tubulointerstitial damage, and glomerular necrosis and increases in glomerular filtration rate and renal plasma flow. In conclusion, antioxidant treatment of high-Na Dahl S rats decreased renal inflammatory cytokines and chemokines, renal immune cells, NF-B, and arterial pressure and improved renal function and damage. renal failure; cytokines; chemokines; renal hemodynamics; salt-sensitivity; nuclear factor-B STUDIES IN HUMAN AND EXPERIMENTAL HYPERTENSION have shown that increases in oxidative stress may play an important role in the etiology and maintenance of increased blood pressure. Increased oxidative stress has been found in the spontaneously hypertensive rat (SHR), the stroke-prone SHR, DOCA-salt hypertensive rats, and the Dahl salt-sensitive (S) rat (5,6,10,21,22,41,49). In addition, evidence for increased renal oxidative stress has been found in lead-induced hypertension (48), coarctation of the aorta (3), and in the Dahl S rat (22, 43).There is considerable evidence for the involvement of the immune system in hypertension. Studies in several models of experimental hypertension have found renal invasion of lymphocytes and macrophages (24,29,31,40,45). Anti-immune therapy administered to these models of hypertension successfully decreased arterial pressure (32) and renal levels of immunocompetent cells.Our laboratory has shown that the Dahl S rat, when challenged with a high-salt diet, experiences both oxidative stress and inflammation (45), and this is associated with hypertension and considerable r...

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N-Acetylcysteine improves renal dysfunction, ameliorates kidney damage and decreases blood pressure in salt-sensitive hypertension

Cited by 43 publications

References 35 publications

The role of oxidative stress in the pathophysiology of hypertension

The role of oxidative stress in the pathophysiology of hypertension

Lipid Peroxidation and Antioxidants in Arterial Hypertension

Interactions between oxidative stress and inflammation in salt-sensitive hypertension

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