Oxidative Stress Increases Synthesis of Big Endothelin-1 by Activation of the Endothelin-1 Promoter

Kähler, Jan; Mendel, Sabine; Weckmüller, Jörn; Orzechowski, Hans‐Dieter; Mittmann, Clemens; Köster, Ralf; Paul, Martin; Meinertz, Thomas; Münzel, Thomas

doi:10.1006/jmcc.2000.1178

Cited by 144 publications

(107 citation statements)

References 29 publications

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“…Increased superoxide production was observed in all layers of the vascular wall, namely the endothelium, media and adventitia, 14 and may also increase vasoconstrictor tone via stimulation of the expression of endothelin-1 in the smooth muscle and endothelial cell layer. 109,110 Acute or chronic treatment with antioxidants or superoxide dismutase not only improved endothelial dysfunction but also markedly reduced blood pressure, indicating the potential role of ROS in the initiation and maintenance of hypertension.…”

Section: Ros Sources In Hypertension Nadph Oxidasesmentioning

confidence: 99%

Oxidative stress and endothelial dysfunction in hypertension

2011

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Systemic arterial hypertension is a highly prevalent cardiovascular risk factor that causes significant morbidity and mortality, and is becoming an increasingly common health problem because of the increasing longevity and prevalence of predisposing factors such as sedentary lifestyle, obesity and nutritional habits. Further complicating the impact of this disease, mild and moderate hypertension are usually asymptomatic, and their presence (and the subsequent increase in cardiovascular risk) is often unrecognized. The pathophysiology of hypertension involves a complex interaction of multiple vascular effectors including the activation of the sympathetic nervous system, of the renin-angiotensin-aldosterone system and of the inflammatory mediators. Subsequent vasoconstriction and inflammation ensue, leading to vessel wall remodeling and, finally, to the formation of atherosclerotic lesions as the hallmark of advanced disease. Oxidative stress and endothelial dysfunction are consistently observed in hypertensive subjects, but emerging evidence suggests that they also have a causal role in the molecular processes leading to hypertension. Reactive oxygen species (ROS) may directly alter vascular function or cause changes in vascular tone by several mechanisms including altered nitric oxide (NO) bioavailability or signaling. ROS-producing enzymes involved in the increased vascular oxidative stress observed during hypertension include the NADPH oxidase, xanthine oxidase, the mitochondrial respiratory chain and an uncoupled endothelial NO synthase. In the current review, we will summarize our current understanding of the molecular mechanisms in the development of hypertension with an emphasis on oxidative stress and endothelial dysfunction.

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Section: Ros Sources In Hypertension Nadph Oxidasesmentioning

confidence: 99%

Oxidative stress and endothelial dysfunction in hypertension

2011

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“…The production of endothelin is stimulated by both angiotensin II and oxidative stress in endothelial and smooth muscle cells. [57][58][59] An increased endothelin-1-like and big endothelin-1-like immunoreactivity in the tunica media of tolerant vessels has been demonstrated during nitrate treatment in two different animal models. 60,61 In one report, exposure of normal vessels to low concentrations of endothelin-1 caused a hypersensitivity to vasoconstricting agents similar to that observed in nitrate tolerant vessels.…”

Section: Neurohormonal Activation and The Control Of ·O 2 ؊ Productionmentioning

confidence: 99%

The Puzzle of Nitrate Tolerance

Gori

Parker

2002

Circulation

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“…NTG-induced increases in oxidative stress could also lead to increased production of endothelin-1 within endothelial and smooth muscle cells, leading to PKC activation, which in turn may trigger enhanced constrictor responses to almost every receptor-dependent agonist. [23][24][25] Finally, NTG tolerance-induced superoxide and peroxynitrite formation could also interfere with nitrovasodilator action at the level of soluble guanylyl cyclase (sGC). 26,27 This inhibition of sGC in nitrate tolerance may contribute to reduced NO bioavailability to NTG.…”

Section: Discussionmentioning

confidence: 99%

Effect of Pioglitazone on Nitroglycerin-Induced Impairment of Nitric Oxide Bioavailability by a Catheter-Type Nitric Oxide Sensor

Ikejima

Imanishi

Tsujioka

et al. 2008

Circ J

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everal clinical and basic studies have shown that chronic treatment with nitroglycerin (NTG) causes endothelial dysfunction. [1][2][3] However, the limitation of these data is that the release of nitric oxide (NO) from the endothelium was estimated on the basis of the comparison of vessel relaxation. We have very recently shown that longterm treatment of New Zealand White rabbits with NTG decreases basal, as well as acetylcholine (ACh)-induced plasma NO concentrations by using a catheter-type NO sensor, accompanied with augmentation of nitrosative stress. 4 In addition, we have shown that the negative effects of NTG could be prevented by co-treatment with drugs attenuating nitrosative stress, such as, angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers (ARB). 4 The peroxisome proliferator-activated receptor (PPAR) is a nuclear receptor that has recently emerged as a pivotal intracellular controller of systemic and vascular processes, including inflammation and atherosclerosis. 5 PPAR is expressed in all major cell types involved in the initiation and evolution of the atherosclerotic plaque, including endothelial cells, vascular smooth muscle cells, macrophages, and T lymphocytes, where it might exert anti-inflammatory and potentially anti-atherogenic effects. 6 Interestingly, PPAR stimulation improves insulin resistance as well as endothelial function in patients with type 2 diabetes. 7 However, it is unknown whether this beneficial effect of PPAR stimulation on endothelial function could extend to NTG-induced endothelial dysfunction. It is clinically important because patients with diabetes mellitus have frequently accompanied with ischemic heart disease.By using the catheter-type NO sensor we investigated to clarify the effect of PPAR agonist on the impairment of bioavailability of NO induced by chronic treatment with NTG patches. The present study has shown that the NTGinduced impairment of NO bioavailability is significantly reversed by the co-treatment with a PPAR agonist, pioglitazone. Methods A Catheter Type NO SensorIntegrated architecture and performance of the cathetertype NO sensor have been described previously. [8][9][10] In brief, an NO sensor (amino-700 XL, Innovative Instruments, 700 m in diameter at the detection tip) was mounted in a 4-Fr catheter (1,200 mm long; Hirakawa Hewtech, Tokyo, Japan) and fixed with silicon adhesive. The oxidative current of NO was monitored by with an NO monitor (model inNO-T, Innovative Instruments). Each sensor was calibrated by using an NO-saturated pure water as previously described. [8][9][10] Briefly, NO-saturated pure water was prepared by bubbling pure NO gas in oxygen-free pure water. Using a gas-tight syrindge, 5 l was injected into a well Background We examined whether nitroglycerin (NTG)-induced impairment of nitric oxide (NO) bioavailability could be modified by a peroxisome proliferator-activated receptor (PPAR) agonist. Methods and ResultsMale New Zealand White rabbits were treated for 7 days with NTG patches, either al...

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Oxidative Stress Increases Synthesis of Big Endothelin-1 by Activation of the Endothelin-1 Promoter

Cited by 144 publications

References 29 publications

Oxidative stress and endothelial dysfunction in hypertension

Oxidative stress and endothelial dysfunction in hypertension

The Puzzle of Nitrate Tolerance

Effect of Pioglitazone on Nitroglycerin-Induced Impairment of Nitric Oxide Bioavailability by a Catheter-Type Nitric Oxide Sensor

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