Tetrahydrobiopterin, L-Arginine and Vitamin C Act Synergistically to Decrease Oxidative Stress, Increase Nitric Oxide and Improve Blood Flow after Induction of Hindlimb Ischemia in the Rat

Cardiac defects associated with increased pulmonary blood flow result in pulmonary vascular dysfunction that may relate to a decrease in bioavailable nitric oxide (NO). An 8-mm graft (shunt) was placed between the aorta and pulmonary artery in 30 late gestation fetal lambs; 27 fetal lambs underwent a sham procedure. Hemodynamic responses to ACh (1 μg/kg) and inhaled NO (40 ppm) were assessed at 2, 4, and 8 wk of age. Lung tissue nitric oxide synthase (NOS) activity, endothelial NOS (eNOS), neuronal NOS (nNOS), inducible NOS (iNOS), and heat shock protein 90 (HSP90), lung tissue and plasma nitrate and nitrite (NOx), and lung tissue superoxide anion and nitrated eNOS levels were determined. In shunted lambs, ACh decreased pulmonary artery pressure at 2 wk ( P < 0.05) but not at 4 and 8 wk. Inhaled NO decreased pulmonary artery pressure at each age ( P < 0.05). In control lambs, ACh and inhaled NO decreased pulmonary artery pressure at each age ( P < 0.05). Total NOS activity did not change from 2 to 8 wk in control lambs but increased in shunted lambs (ANOVA, P < 0.05). Conversely, NOxlevels relative to NOS activity were lower in shunted lambs than controls at 4 and 8 wk ( P < 0.05). eNOS protein levels were greater in shunted lambs than controls at 4 wk of age ( P < 0.05). Superoxide levels increased from 2 to 8 wk in control and shunted lambs (ANOVA, P < 0.05) and were greater in shunted lambs than controls at all ages ( P < 0.05). Nitrated eNOS levels were greater in shunted lambs than controls at each age ( P < 0.05). We conclude that increased pulmonary blood flow results in progressive impairment of basal and agonist-induced NOS function, in part secondary to oxidative stress that decreases bioavailable NO.

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Role of Oxidative Stress and Mitochondrial Dysfunction in Sepsis and Potential Therapies

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/5985209 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 53

Author(s):

Konstantinos Mantzarlis ◽

Vasiliki Tsolaki ◽

Epaminondas Zakynthinos

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Intensive Care ◽

Vitamin C ◽

Causes Of Death ◽

Redox Balance ◽

Cardiac Performance ◽

Efficiency Evaluation ◽

Permeability Impairment

Sepsis is one of the most important causes of death in intensive care units. Despite the fact that sepsis pathogenesis remains obscure, there is increasing evidence that oxidants and antioxidants play a key role. The imbalance of the abovementioned substances in favor of oxidants is called oxidative stress, and it contributes to sepsis process. The most important consequences are vascular permeability impairment, decreased cardiac performance, and mitochondrial malfunction leading to impaired respiration. Nitric oxide is perhaps the most important and well-studied oxidant. Selenium, vitamin C, and 3N-acetylcysteine among others are potential therapies for the restoration of redox balance in sepsis. Results from recent studies are promising, but there is a need for more human studies in a clinical setting for safety and efficiency evaluation.

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Effects of treadmill training combined with Vitamin C or estradiol on Nitric Oxide metabolite, oxidative stress marker and liver enzymes levels in rat

hormozgan medical journal ◽

10.29252/hmj.22.1.18 ◽

2018 ◽

Vol 22 (1) ◽

pp. 18-24

Author(s):

Maryam Abbasi Darehbidi ◽

Effat Bambaeichi ◽

Mehdi Nematbakhsh ◽

◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Vitamin C ◽

Liver Enzymes ◽

Treadmill Training ◽

Oxidative Stress Marker ◽

Stress Marker

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Lack of effect of oral vitamin C on blood pressure, oxidative stress and endothelial function in Type II diabetes

Clinical Science ◽

10.1042/cs1030339 ◽

2002 ◽

Vol 103 (4) ◽

pp. 339-344 ◽

Cited By ~ 91

Author(s):

D. DARKO ◽

A. DORNHORST ◽

F.J. KELLY ◽

J.M. RITTER ◽

P.J. CHOWIENCZYK

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Blood Flow ◽

Vitamin C ◽

Endothelial Function ◽

Type Ii Diabetes ◽

Forearm Blood Flow ◽

Plasma Concentrations ◽

Type Ii ◽

Oral Vitamin

Type II diabetes is characterized by increased oxidative stress, endothelial dysfunction and hypertension. We investigated whether short-term treatment with oral vitamin C reduces oxidative stress and improves endothelial function and blood pressure in subjects with Type II diabetes. Subjects (n = 35) received vitamin C (1.5g daily in three doses) or matching placebo for 3 weeks in a randomized, double-blind, parallel-group design. Plasma concentrations of 8-epi-prostaglandin F2α (8-epi-PGF2α), a non-enzymically derived oxidation product of arachidonic acid, were used as a marker of oxidative stress. Endothelial function was assessed by measuring forearm blood flow responses to brachial artery infusion of the endothelium-dependent vasodilator acetylcholine (with nitroprusside as an endothelium-independent control) and by the pulse wave responses to systemic albuterol (endothelium-dependent vasodilator) and glyceryl trinitrate (endothelium-independent vasodilator). Plasma concentrations of vitamin C increased from 58±6 to 122±10μmol/l after vitamin C, but 8-epi-PGF2α levels (baseline, 95±4pg/l; after treatment, 99±5pg/l), blood pressure (baseline, 141±5/80±2mmHg; after treatment, 141±5/81±3mmHg) and endothelial function, as assessed by the systemic vasodilator response to albuterol and by the forearm blood flow response to acetylcholine, were not significantly different from baseline or placebo. Thus treatment with vitamin C (1.5 g daily) for 3 weeks does not significantly improve oxidative stress, blood pressure or endothelial function in patients with Type II diabetes.

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Exercise-Induced Blood Flow Decreases Endothelial Oxidative Stress and Upregulates Endothelial Nitric Oxide Synthase

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000402076.84222.37 ◽

2011 ◽

Vol 43 (Suppl 1) ◽

pp. 746-747

Author(s):

Alvaro N. Gurovich ◽

Elizabeth H. Zeanah ◽

Joseph C. Avery ◽

Barbara Gomez ◽

Randy W. Braith

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Blood Flow ◽

Nitric Oxide Synthase ◽

Endothelial Nitric Oxide Synthase ◽

Exercise Induced ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

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Moderate hyperbilirubinemia improves renal hemodynamics in ANG II-dependent hypertension

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00316.2010 ◽

2010 ◽

Vol 299 (4) ◽

pp. R1044-R1049 ◽

Cited By ~ 25

Author(s):

Trinity Vera ◽

David E. Stec

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Blood Pressure ◽

Blood Flow ◽

Antisense Oligonucleotides ◽

Filtration Rate ◽

Renal Hemodynamics ◽

Blood Levels ◽

Ang Ii ◽

Osmotic Minipump

We have previously demonstrated that moderate hyperbilirubinemia decreases blood pressure in ANG II-dependent hypertension through mechanisms that decrease oxidative stress and increase nitric oxide levels. Since decreases in renal hemodynamics play an important role in mediating the hypertensive actions of ANG II, the goal of the present study was to examine the effect of moderate hyperbilirubinemia on glomerular filtration rate (GFR) and renal blood flow (RBF) in a mouse model of ANG II hypertension. Mice were made moderately hyperbilirubinemic by two methods: indinavir or specific morpholino antisense oligonucleotides against UGT1A1, which is the enzyme responsible for the conjugation of bilirubin in the liver. GFR and RBF were measured in mice after implantation of an osmotic minipump delivering ANG II at a rate of 1 μg·kg−1·min−1. GFR was measured by continuous infusion of I125-labeled iothalamate on days 5 and 6 of ANG II infusion in conscious mice. RBF was measured on day 7 of ANG II infusion in anesthetized mice. Blood levels of unconjugated bilirubin were significantly increased in mice treated with indinavir or anti-UGT1A1 ( P = 0.002). ANG II decreased GFR by 33% of control ( n = 9, P = 0.004), and this was normalized by moderate hyperbilirubinemia ( n = 6). Next, we examined the effect of moderate hyperbilirubinemia on RBF in ANG II-infused mice. ANG II infusion significantly decreased RBF by 22% ( P = 0.037) of control, and this decrease was normalized by moderate hyperbilirubinemia ( n = 6). These results indicate that improvement of renal hemodynamics may be one mechanism by which moderate hyperbilirubinemia lowers blood pressure in this model.

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Wie altern Gefäße? Mechanismen und klinische Implikationen

VASA ◽

10.1024/0301-1526.33.1.3 ◽

2004 ◽

Vol 33 (1) ◽

pp. 3-11 ◽

Cited By ~ 9

Author(s):

van der Loo ◽

Koppensteiner ◽

Lüscher

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Vitamin E ◽

Nitric Oxide Synthase ◽

Vitamin C ◽

Oxide Synthase ◽

Klinische Implikationen

Altern ist ein wichtiger kardialer und vaskulärer Risikofaktor. Für das Gefäßaltern sind genetische, mechanische und hämodynamische Faktoren ausschlaggebend. So sind altersabhängige Veränderungen in Gefäßen, welche weniger Pulsatilität und Blutdruck ausgesetzt sind, wie Kapillaren und Venen, geringer oder abwesend. Vor allem in den großen Widerstandsgefäßen kommt es im Laufe des Alterns morphologisch zu einer Intima- und Mediaverdickung, verknüpft mit einer vermehrten Einlagerung von Matrixsubstanzen, und letztlich resultierend in verminderter Compliance der Gefäße. Es lassen sich Funktionsstörungen des Endothels nachweisen. Hier kommt es zu einer deutlichen Heraufregulierung der endothelialen Nitric Oxide Synthase (eNOS), welche für die Produktion des endogenen Vasodilatators Nitric Oxide (NO) verantwortlich ist. Paradoxerweise sind trotzdem die Vasorelaxationen im Alter vermindert, da es gleichzeitig zu einer erhöhten Produktion freier Radikale, im Besonderen Superoxid (O2-) kommt. O2- und NO bilden in einer schnell ablaufenden chemischen Reaktion Peroxinitrit (ONOO-), welches Proteine nitriert. Durch diese Nitrierung kommt es zur funktionellen Beeinträchtigung dieser Proteine, so dass verschiedene Signalübertragungswege, z.B. Tyrosilierung von Enzymen, blockiert werden. Primärer Ort der Bildung freier Sauerstoffradikale sind die endothelialen Mitochondrien. Bislang ungeklärt ist, ob der oxidative Stress als ein zentrales Ereignis des Gefäßalterns pharmakologisch beeinflussbar ist. Hier standen vor allem antioxidativ wirkende Vitamine im Mittelpunkt des Interesses. Überraschenderweise wird jedoch Vitamin E im Tiermodell vermehrt mit steigendem Alter in der aortalen Wand eingelagert, was im Rahmen eines altersassoziierten gegenregulatorischen Mechanismus zur Abwendung des vermehrten oxidativen Stresses erfolgt. Umgekehrt ist Vitamin C signifikant vermindert. Es bleibt abzuwarten, ob das Gefäßaltern durch Vitamin C oder andere Antioxidantien günstig beeinflusst werden kann. Für Statine und ACE-Hemmer wurden schon Wirkungen beschrieben, die mit Schlüsselmechanismen des Gefäßalterungsprozesses interferieren. Die Entwicklung therapeutischer Interventionen zur Verlangsamung des Gefäßalterns wird für das Auftreten von Herz- und Gefäßerkrankungen im Alter in Zukunft große Bedeutung haben.

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