Punicalagin Prevents Hypoxic Pulmonary Hypertension via Anti-Oxidant Effects in Rats

2016 ◽  
Vol 44 (04) ◽  
pp. 785-801 ◽  
Author(s):  
Jingyun Shao ◽  
Peng Wang ◽  
An Liu ◽  
Xusheng Du ◽  
Jie Bai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Hypertension ◽  
Endothelial Dysfunction ◽  
Pulmonary Arteries ◽  
Pomegranate Juice ◽  
No Production ◽  
Protective Effects ◽  
Hypoxic Pulmonary Hypertension ◽  
Beneficial Effects ◽  
Anti Oxidant

Punicalagin (PG), a major bioactive ingredient in pomegranate juice, has been proven to have anti-oxidative stress properties and to exert protective effects on acute lung injuries induced by lipopolysaccharides. This study aimed to investigate the effects of PG treatment on hypoxic pulmonary hypertension (HPH) and the underlying mechanisms responsible for the effects. Rats were exposed to 10% oxygen for 2 wk (8 h/day) to induce the HPH model. PG (5, 15, 45[Formula: see text]mg/kg) was orally administered 10[Formula: see text]min before hypoxia each day. PG treatments at the doses of 15 and 45[Formula: see text]mg/kg/d decreased the mean pulmonary arterial pressure (mPAP) and alleviated right ventricular hypertrophy and vascular remodeling in HPH rats. Meanwhile, PG treatment attenuated the hypoxia-induced endothelial dysfunction of pulmonary artery rings. The beneficial effects of PG treatment were associated with improved nitric oxide (NO)-cGMP signaling and reduced oxidative stress, as evidenced by decreased superoxide generation, gp91[Formula: see text] expression and nitrotyrosine content in the pulmonary arteries. Furthermore, tempol’s scavenging of oxidative stress also increased NO production and attenuated endothelial dysfunction and pulmonary hypertension in HPH rats. Combining tempol and PG did not exert additional beneficial effects compared to tempol alone. Our study indicated for the first time that PG treatment can protect against hypoxia-induced endothelial dysfunction and pulmonary hypertension in rats, which may be induced via its anti-oxidant actions.

scholarly journals Pentaerythritol Tetranitrate In Vivo Treatment Improves Oxidative Stress and Vascular Dysfunction by Suppression of Endothelin-1 Signaling in Monocrotaline-Induced Pulmonary Hypertension

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Sebastian Steven ◽  
Matthias Oelze ◽  
Moritz Brandt ◽  
Elisabeth Ullmann ◽  
Swenja Kröller-Schön ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Hypertension ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Whole Blood ◽  
Pulmonary Arteries ◽  
Vascular Wall ◽  
Pentaerythritol Tetranitrate ◽  
Endothelin 1 ◽  
Pulmonary Arterial

Objective. Oxidative stress and endothelial dysfunction contribute to pulmonary arterial hypertension (PAH). The role of the nitrovasodilator pentaerythritol tetranitrate (PETN) on endothelial function and oxidative stress in PAH has not yet been defined.Methods and Results. PAH was induced by monocrotaline (MCT, i.v.) in Wistar rats. Low (30 mg/kg; MCT30), middle (40 mg/kg; MCT40), or high (60 mg/kg; MCT60) dose of MCT for 14, 28, and 42 d was used. MCT induced endothelial dysfunction, pulmonary vascular wall thickening, and fibrosis, as well as protein tyrosine nitration. Pulmonary arterial pressure and heart/body and lung/body weight ratio were increased in MCT40 rats (28 d) and reduced by oral PETN (10 mg/kg, 24 d) therapy. Oxidative stress in the vascular wall, in the heart, and in whole blood as well as vascular endothelin-1 signaling was increased in MCT40-treated rats and normalized by PETN therapy, likely by upregulation of heme oxygenase-1 (HO-1). PETN therapy improved endothelium-dependent relaxation in pulmonary arteries and inhibited endothelin-1-induced oxidative burst in whole blood and the expression of adhesion molecule (ICAM-1) in endothelial cells.Conclusion. MCT-induced PAH impairs endothelial function (aorta and pulmonary arteries) and increases oxidative stress whereas PETN markedly attenuates these adverse effects. Thus, PETN therapy improves pulmonary hypertension beyond its known cardiac preload reducing ability.

Protective Effects of Pomegranate in Endothelial Dysfunction

2020 ◽  
Vol 26 (30) ◽  
pp. 3684-3699 ◽  
Author(s):  
Nathalie T.B. Delgado ◽  
Wender N. Rouver ◽  
Roger L. dos Santos
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Common Factor ◽  
Blood Lipid ◽  
Punica Granatum ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Anti Inflammatory

Background: Punica granatum L. is an infructescence native of occidental Asia and Mediterranean Europe, popularly referred to as pomegranate. It has been used in ethnomedicine for several applications, including the treatment of obesity, inflammation, diabetes, and the regulation of blood lipid parameters. Thus, pomegranate has been linked to the treatment of cardiovascular diseases that have endothelial dysfunction as a common factor acting mainly against oxidative stress due to its high polyphenol content. Its biocomponents have antihypertensive, antiatherogenic, antihyperglycemic, and anti-inflammatory properties, which promote cardiovascular protection through the improvement of endothelial function. Methods: Different electronic databases were searched in a non-systematic way to uncover the literature of interest. Conclusion: This review article presents updated information on the role of pomegranate in the context of endothelial dysfunction and cardiovascular diseases. We have shown that pomegranate, or rather its components (e.g., tannins, flavonoids, phytoestrogens, anthocyanins, alkaloids, etc.), have beneficial effects on the cardiovascular system, improving parameters such as oxidative stress and the enzymatic antioxidant system, reducing reactive oxygen species formation and acting in an anti-inflammatory way. Thus, this review may contribute to a better understanding of pomegranate's beneficial actions on endothelial function and possibly to the development of strategies associated with conventional treatments of cardiovascular diseases.

scholarly journals Tongxinluo Prevents Endothelial Dysfunction Induced by Homocysteine ThiolactoneIn Vivovia Suppression of Oxidative Stress

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yi Zhang ◽  
Tiecheng Pan ◽  
Xiaoxuan Zhong ◽  
Cai Cheng
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Ex Vivo ◽  
Umbilical Vein ◽  
Protective Effects ◽  
Sod Activity ◽  
Homocysteine Thiolactone ◽  
Beneficial Effects ◽  
Umbilical Vein Endothelial Cells

Aim. To explore whether Chinese traditional medicine, tongxinluo (TXL), exerts beneficial effects on endothelial dysfunction induced by homocysteine thiolactone (HTL) and to investigate the potential mechanisms.Methods and Results. Incubation of cultured human umbilical vein endothelial cells with HTL (1 mM) for 24 hours significantly reduced cell viabilities assayed by MTT, and enhanced productions of reactive oxygen species. Pretreatment of cells with TXL (100, 200, and 400 μg/mL) for 1 hour reversed these effects induced by HTL. Further, coincubation with GW9662 (0.01, 0.1 mM) abolished the protective effects of TXL on HTL-treated cells. Inex vivoexperiments, exposure of isolated aortic rings from rats to HTL (1 mM) for 1 hour dramatically impaired acetylcholine-induced endothelium-dependent relaxation, reduced SOD activity, and increased malondialdehyde content in aortic tissues. Preincubation of aortic rings with TXL (100, 200, and 400 μg/mL) normalized the disorders induced by HTL. Importantly, all effects induced by TXL were reversed by GW9662.In vivoanalysis indicated that the administration of TXL (1.0 g/kg/d) remarkably suppressed oxidative stress and prevented endothelial dysfunction in rats fed with HTL (50 mg/kg/d) for 8 weeks.Conclusions. TXL improves endothelial functions in rats fed with HTL, which is related to PPARγ-dependent suppression of oxidative stress.

Short-term exposure to cigarette smoke induces endothelial dysfunction in small intrapulmonary arteries: analysis using guinea pig precision cut lung slices

2008 ◽  
Vol 104 (5) ◽  
pp. 1462-1469 ◽  
Author(s):  
J. L. Wright ◽  
A. Churg
Keyword(s):  
Pulmonary Hypertension ◽  
Endothelial Dysfunction ◽  
Cigarette Smoke ◽  
Pulmonary Arteries ◽  
Delayed Response ◽  
No Production ◽  
Short Term ◽  
No Donor ◽  
Short Term Exposure ◽  
Precision Cut Lung Slices

The pathogenesis of cigarette smoke-induced pulmonary hypertension is not understood. We have previously shown that smoke rapidly and persistently, but discoordinately, upregulates gene expression of mediators that control vasoconstriction, vasoproliferation, and vasorelaxation in small intrapulmonary arteries. To investigate the possibility that smoke also induces endothelial dysfunction, a finding common to other forms of pulmonary hypertension, we exposed guinea pigs to smoke or air (control) daily for 2 wk and then prepared precision-cut lung slices. After exposure to endothelin-1, a vasoconstrictor, intra-acinar arteries in lung slices derived from smoke-exposed animals constricted more rapidly (greater constriction at a given concentration of endothelin) than did vessels from air-exposed animals. To examine relaxation responses, arteries were constricted with the vasconstrictor U-46619 and then relaxed with progressively increasing doses of acetylcholine. Vessels from smokers had a delayed response to acetylcholine compared with vessels from controls. The NO synthase inhibitor NG-nitro-l-arginine methyl ester reduced relaxation in both control and smoke-exposed arteries, whereas the NO donor sodium nitroprusside increased relaxation of the smoke-exposed arteries, confirming that endothelial dysfunction with decreased effective NO production is present. These findings show that precision cut lung slices can be used to examine the physiological effects of cigarette smoke on intra-acinar pulmonary arteries and indicate that even relatively short-term exposure to smoke produces endothelial dysfunction with a resulting tendency to earlier constriction and later relaxation in cigarette smokers. These changes may be important in the development of pulmonary hypertension.

Clinical aspects of reactive oxygen and nitrogen species

2004 ◽  
Vol 71 ◽  
pp. 121-133 ◽  
Author(s):  
Ascan Warnholtz ◽  
Maria Wendt ◽  
Michael August ◽  
Thomas Münzel
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Vascular Tissue ◽  
Rapid Development ◽  
Reactive Oxygen ◽  
Clinical Aspects ◽  
No Production ◽  
Oxygen Species

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.

Pharmacological study on the possible involvement of a Nrf2 -Heme oxygenase pathways in anti-cataract activity of fisetin

2020 ◽  
Vol 10 (1) ◽  
pp. 14-19
Author(s):  
Krishna Reddy BV ◽  
Avinash Kumar Reddy G ◽  
Sujitha V ◽  
Manasa A
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Pharmacological Study ◽  
World Population ◽  
Central Feature ◽  
Beneficial Effects ◽  
Radical Production ◽  
Anti Oxidant ◽  
Diabetic Population ◽  
Oxidant Status

DM otherwise diabetes is now a days an epidemic with the percentage of patient population rising to almost 10% of the world population. Out of all the DM complications, cataract leads the way contributing to disabilities to about 60% of diabetic population. But the pathogenesis of DM cataract is still a half-understood area of medicine there by posing a problem in the therapy. The data that we have till now gives us enough evidence to advocate the oxidative stress has a major role for the pathogenesis of DM complications like DMnephropathy, DMneuropathy, and cardiac hypertrophy, which suggests the oxidative stress is a central feature of diabetes. In the current research, the pharmacological evaluation of Fisetin for its DM based anti-cataract property was performed. This research concentrates to estimate the possible involvement of Nrf-2 / heme oxygenase (HO)-pathway in the observed therapeutic effect, if any. The data obtained in this study also indicate that the observed beneficial effects mainly due to activation of Nrf2/HO-1 pathway. These effects probably result in increased tissue anti-oxidant status as well as decreased free radical production, which ultimately responsible for the observed beneficial effects of Fisetin against hyperglycemia-induced cataract.

scholarly journals Dehydroepiandrosterone promotes pulmonary artery relaxation by NADPH oxidation-elicited subunit dimerization of protein kinase G 1α

2014 ◽  
Vol 306 (4) ◽  
pp. L383-L391 ◽  
Author(s):  
Dhara Patel ◽  
Sharath Kandhi ◽  
Melissa Kelly ◽  
Boon Hwa Neo ◽  
Michael S. Wolin
Keyword(s):  
Pulmonary Hypertension ◽  
Protein Kinase ◽  
Pulmonary Arteries ◽  
Activation Mechanism ◽  
Protein Kinase G ◽  
Beneficial Effects ◽  
Vasp Phosphorylation ◽  
Vasodilator Activity ◽  
Nadph Oxidation ◽  
Knockin Mouse

The activity of glucose-6-phosphate dehydrogenase (G6PD) controls a vascular smooth muscle relaxing mechanism promoted by the oxidation of cytosolic NADPH, which has been associated with activation of the 1α form of protein kinase G (PKG-1α) by a thiol oxidation-elicited subunit dimerization. This PKG-1α-activation mechanism appears to contribute to responses of isolated endothelium-removed bovine pulmonary arteries (BPA) elicited by peroxide, cytosolic NADPH oxidation resulting from G6PD inhibition, and hypoxia. Dehydroepiandrosterone (DHEA) is a steroid hormone with pulmonary vasodilator activity, which has beneficial effects in treating pulmonary hypertension. Because multiple mechanisms have been suggested for the vascular effects of DHEA and one of the known actions of DHEA is inhibiting G6PD, we investigated whether it promoted relaxation associated with NADPH oxidation, PKG-1α dimerization, and PKG activation detected by increased vasodilator-stimulated phosphoprotein (VASP) phosphorylation. Relaxation of BPA to DHEA under aerobic or hypoxic conditions was associated with NADPH oxidation, PKG-1α dimerization, and increased VASP phosphorylation. The vasodilator activity of DHEA was markedly attenuated in pulmonary arteries and aorta from a PKG knockin mouse containing a serine in place of a cysteine involved in PKG dimerization. DHEA promoted increased PKG dimerization in lungs from wild-type mice, which was not detected in the PKG knockin mouse model. Thus PKG-1α dimerization is a major contributing factor to the vasodilator actions of DHEA and perhaps its beneficial effects in treating pulmonary hypertension.

scholarly journals Oxidative Stress and Endothelial Dysfunction in Pulmonary Arteries of Aged Rats

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Zoltan Ungvari ◽  
Praveen Ballabh ◽  
Andrej Podlutsky ◽  
Anna Csiszar
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Pulmonary Arteries ◽  
Aged Rats

scholarly journals Notoginsenoside R1 Ameliorates Diabetic Retinopathy through PINK1-Dependent Activation of Mitophagy

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 213 ◽  
Author(s):  
Ping Zhou ◽  
Weijie Xie ◽  
Xiangbao Meng ◽  
Yadong Zhai ◽  
Xi Dong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Oral Treatment ◽  
Müller Cells ◽  
Panax Notoginseng ◽  
Protective Effects ◽  
Muller Cells ◽  
Beneficial Effects ◽  
Pre Treatment ◽  
Lc3 Puncta

: Accumulating evidence has indicated that inflammation, oxidative stress, apoptosis, and autophagy in retinal Müller cells are involved in diabetic retinopathy (DR). Notoginsenoside R1 (NGR1), a novel saponin extracted from Panax notoginseng, posesses pharmacological properties, including treating diabetic encephalopathy and improving microcirculatory disorders. Nevertheless, its beneficial effects on DR and the potential mechanism remain to be elucidated. In this study, we found retinal vascular degeneration, reduced retinal thickness, and impaired retinal function in db/db mice were all dramatically attenuated by oral treatment with NGR1 (30 mg/kg) for 12 weeks. NGR1 pretreatment also significantly inhibited apoptosis, markedly suppressed the VEGF expression, markedly increased PEDF expression and markedly inhibited oxidative stress and inflammation in rat retinal Müller cells (rMC-1) subjected to high glucose (HG) and in the retinas of db/db mice. Furthermore, NGR1 pre-treatment upregulated the level of PINK1 and Parkin, increased the LC3-II/LC3-I ratio, and downregulated the level of p62/SQSTM1 in rMC-1 cells induced by HG and in the retinas of db/db mice. Moreover, NGR1 administration enhanced the co-localization of GFP-LC3 puncta and MitoTracker in rMC-1 cells. Importantly, knockdown of PINK1 abolished the protective effects of NGR1. In conclusion, these phenomena suggested that NGR1 prevented DR via PINK1-dependent enhancement of mitophagy.

Neutral endopeptidase inhibition attenuates development of hypoxic pulmonary hypertension in rats

1993 ◽  
Vol 75 (4) ◽  
pp. 1615-1623 ◽  
Author(s):  
J. R. Klinger ◽  
R. D. Petit ◽  
R. R. Warburton ◽  
D. S. Wrenn ◽  
F. Arnal ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Pulmonary Arteries ◽  
Systolic Pressure ◽  
Weight Ratio ◽  
Neutral Endopeptidase ◽  
Mrna Levels ◽  
Hypoxic Pulmonary Hypertension ◽  
Ventricular Systolic Pressure ◽  
Nep Inhibition

Neutral endopeptidase (NEP) inhibition is thought to blunt hypoxic pulmonary hypertension by reducing atrial natriuretic peptide (ANP) metabolism, but this hypothesis has not been confirmed. We measured NEP activity, guanosine 3',5'-cyclic monophosphate (cGMP) production, plasma ANP levels, and cardiac ANP synthesis in rats given an orally active NEP inhibitor (SCH-34826) during 3 wk of hypoxia. Under normoxic conditions, SCH-34826 had no effect on plasma ANP levels but reduced pulmonary and renal NEP activity by 50% and increased urinary cGMP levels (60 +/- 6 vs. 22 +/- 4 pg/mg creatinine; P < 0.05). Under hypoxic conditions, SCH-34826-treated rats had lower plasma ANP levels (1,259 +/- 361 vs. 2,101 +/- 278 pg/ml; P < 0.05), lower right ventricular systolic pressure (53 +/- 5 vs. 73 +/- 2 mmHg; P < 0.05), lower right ventricle weight-to-left ventricle+septum weight ratio (0.47 +/- 0.04 vs. 0.53 +/- 0.03; P < 0.05), and less muscularization and percent medial wall thickness of peripheral pulmonary arteries (22 +/- 5 vs. 45 +/- 8% and 17 +/- 1 vs. 25 +/- 1%, respectively; P < 0.05 for all values) than did rats treated with vehicle alone. These values were not affected by SCH-34826 under normoxic conditions. SCH-34826 decreased right ventricular ANP tissue levels in hypoxic rats (27 +/- 10 vs. 8 +/- 1 ng/mg protein; P < 0.05) but did not affect steady-state ANP mRNA levels. We conclude that NEP inhibition blunts pulmonary hypertension without increasing plasma ANP levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Sign in / Sign up

Export Citation Format

Share Document