scholarly journals Vena cava presents endothelial dysfunction prior to thoracic aorta in heart failure: the pivotal role of nNOS uncoupling/ oxidative stress

2021 ◽  
Author(s):  
Patrizia Dardi ◽  
Laís Rossi Perazza ◽  
Gisele Kruger Couto ◽  
Gianne Paul Campos ◽  
Luciano dos Santos Aggum Capettini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Thoracic Aorta ◽  
Vascular Reactivity ◽  
Vena Cava ◽  
Coronary Artery Occlusion ◽  
H2o2 Production ◽  
No Production

Arterial endothelial dysfunction has been extensively studied in heart failure (HF). However little is known about the adjustments shown by the venous system in this condition. Considering that inferior vena cava (VC) tone could influence cardiac performance and HF prognosis, the aim of the present study was to assess the VC and thoracic aorta (TA) endothelial function of HF-post-myocardial infarction (MI) rats, comparing both endothelial responses and signaling pathways developed. Vascular reactivity of TA and VC from HF post-MI and sham operated (SO) rats was assessed with a wire myograph, four weeks after coronary artery occlusion surgery. Nitric oxide (NO), H2O2 production and oxidative stress were evaluated in situ with fluorescent probes, whilst protein expression and dimer/monomer ratio was assessed by western blot. VC from HF rats presented endothelial dysfunction, while TA exhibited higher acetylcholine (ACh)-induced vasodilation when compared to vessels from SO rats. TA exhibited increased ACh-induced NO production due to a higher coupling of endothelial and neuronal NO synthases isoforms (eNOS, nNOS), and enhanced expression of antioxidant enzymes. These adjustments, however, were absent in VC of HF post-MI rats, which exhibited uncoupled nNOS, oxidative stress and higher H2O2 bioavailability. Altogether, this study suggests a differential regulation of endothelial function between VC and TA of HF post-MI rats, most likely due to nNOS uncoupling and compromised antioxidant defense.

scholarly journals MnSOD protects against COX1-mediated endothelial dysfunction in chronic heart failure

2010 ◽  
Vol 298 (5) ◽  
pp. H1600-H1607 ◽  
Author(s):  
Jordan D. Miller ◽  
Veronica A. Peotta ◽  
Yi Chu ◽  
Robert M. Weiss ◽  
Kathy Zimmerman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Function ◽  
Manganese Superoxide Dismutase ◽  
Reduced Ejection Fraction ◽  
Manganese Superoxide ◽  
Cox Inhibitor

Endothelial function is impaired by oxidative stress in chronic heart failure (HF). Mechanisms that protect against increases in oxidative stress in HF are not clear. The goal of this study was to determine whether manganese superoxide dismutase (MnSOD) plays a key role in protecting against endothelial dysfunction in HF. Endothelial function and gene expression were examined in aorta from wild-type mice (MnSOD+/+) and mice deficient in MnSOD (MnSOD+/−) 12 wk after ligation of the left coronary artery (LCA). LCA ligation produced similar size myocardial infarctions in MnSOD+/+ and MnSOD+/− mice and reduced ejection fraction to ∼20% in both groups. Maximal relaxation in response to acetylcholine was 78 ± 3% (mean ± SE) and 66 ± 8% in sham-operated MnSOD+/+ and MnSOD+/− mice, respectively. Expression of antioxidant enzymes increased in MnSOD+/+ mice with HF, and maximal relaxation to acetylcholine was slightly impaired (68 ± 4%). Greater endothelial dysfunction was observed in MnSOD+/− mice with HF (46 ± 5%, P < 0.05), which was significantly improved by polyethylene glycol-catalase but not Tempol. Incubation with the nonspecific cyclooxygenase (COX) inhibitor indomethacin or the COX1 inhibitor valeryl salicylate, but not the COX-2 inhibitor NS-398, significantly improved relaxation to acetylcholine in HF mice (maximum relaxation = 74 ± 5, 91 ± 1, and 58 ± 5%). These data suggest that MnSOD plays a key role in protecting against endothelial dysfunction in HF. A novel mechanism was identified whereby chronic increases in oxidative stress, produced by mitochondrial SOD deficiency, impair vascular function via a hydrogen peroxide-dependent, COX1-dependent, endothelium-derived contracting factor.

scholarly journals Improvement of endothelial dysfunction in experimental heart failure by chronic RAAS-blockade: ACE-inhibition or AT1-receptor blockade?

2001 ◽  
Vol 2 (1_suppl) ◽  
pp. S64-S69 ◽  
Author(s):  
Lodewijk J Wagenaar ◽  
Hendrik Buikema ◽  
Yigal M Pinto ◽  
Wiek H van Gilst
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Heart Failure ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Candesartan Cilexetil ◽  
Ace Inhibition ◽  
At1 Receptor ◽  
Converting Enzyme Inhibitors ◽  
Raas Blockade

Chronic heart failure (CHF) is associated with endothelial dysfunction. Activation of the renin-angiotensin-aldosterone system (RAAS) is believed to be important in the deterioration of endothelial dysfunction in CHF through stimulation of oxidative stress. Whereas angiotensin-converting enzyme inhibitors (ACE-I) improve endothelial function in CHF, the effects of angiotensin II AT1-receptor blockers (ARB) are less well established. Therefore we compared the effects of the ACE-I lisinopril vs. the ARB candesartan on endothelial dysfunction in a rat model of CHF. CHF was induced by myocardial infarction (MI) after coronary ligation. Two weeks after MI, daily treatment with lisinopril (2 mg/kg) or candesartan cilexetil (1.5 mg/kg) was started. After 13 weeks, rats were sacrificed and endothelial function was determined by measuring acetylcholine (ACh)-induced vasodilation in aortic rings, with selective presence of the nitric oxide synthase (NOS)-inhibitor NG-monomethyl-L-arginine (L-NMMA) to determine the contribution of nitric oxide (NO). ACh-induced vasodilation was attenuated in untreated MI (-50%) compared with control rats. This was in part due to an impaired contribution of NO (-49%). Lisinopril and candesartan cilexetil fully normalised ACh-induced dilation, including the part mediated by NO. Chronic RAAS-blockade with lisinopril and candesartan cilexetil normalised endothelial function in CHF in a comparable way. The effect of both treatments included the increase of the NO-mediated dilation, further indicating the important role of oxidative stress in the relationship between the RAAS and endothelial dysfunction in CHF.

Cutaneous vascular reactivity is reduced in aging and in heart failure: association with inflammation

2003 ◽  
Vol 105 (6) ◽  
pp. 699-707 ◽  
Author(s):  
S. E. ANDERSSON ◽  
M.-L. EDVINSSON ◽  
L. EDVINSSON
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Reactivity ◽  
Plasma Concentrations ◽  
Vascular Risk Factors ◽  
Elderly Adults ◽  
Vascular Risk ◽  
Healthy Elderly

In the present study, we have investigated whether changes in vascular reactivity in congestive heart failure (CHF) patients can be detected in the cutaneous microvessels and whether these changes are due to endothelial dysfunction, are affected by increasing age and related to an ongoing inflammation. The responses to local warming and iontophoretically administered endothelium-dependent and -independent vasodilators were investigated in healthy young adults, healthy elderly adults and elderly adults with CHF. The results were correlated with plasma concentrations of vascular risk factors and markers for endothelial dysfunction and inflammation. The vasorelaxant responses were reduced in the elderly groups and were attenuated further in the CHF group. This group also had increases in levels of several markers associated with inflammation, higher blood glucose and homocysteine levels, a lower low-density lipoprotein–cholesterol and a rise in the concentration of von Willebrand factor, indicating a prothrombotic endothelial function. The severity of the heart failure, measured as the plasma level of brain natriuretic peptide, correlated with the intensity of inflammation and to the changes in vascular risk factors and endothelial function. It is concluded that the reactivity of the cutaneous microvessels is reduced with age, and the presence of CHF causes a further impairment. There is endothelial dysfunction in CHF, but it is uncertain to what extent this contributes to the reduced vasodilatory capacity. The inflammatory response appears central for many of the manifestations of the CHF syndrome.

scholarly journals Pathophysiological Association between Diabetes Mellitus and Endothelial Dysfunction

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1306
Author(s):  
Tatsuya Maruhashi ◽  
Yukihito Higashi
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Critical Role ◽  
No Production ◽  
Chronic Hyperglycemia ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Patients With Diabetes ◽  
Glucose Fluctuations

Endothelial dysfunction plays a critical role in atherosclerosis progression, leading to cardiovascular complications. There are significant associations between diabetes mellitus, oxidative stress, and endothelial dysfunction. Oxidative stress is increased by chronic hyperglycemia and acute glucose fluctuations induced by postprandial hyperglycemia in patients with diabetes mellitus. In addition, selective insulin resistance in the phosphoinositide 3-kinase/Akt/endothelial nitric oxide (NO) synthase pathway in endothelial cells is involved in decreased NO production and increased endothelin-1 production from the endothelium, resulting in endothelial dysfunction. In a clinical setting, selecting an appropriate therapeutic intervention that improves or augments endothelial function is important for preventing diabetic vascular complications. Hypoglycemic drugs that reduce glucose fluctuations by decreasing the postprandial rise in blood glucose levels, such as glinides, α-glucosidase inhibitors and dipeptidyl peptidase 4 inhibitors, and hypoglycemic drugs that ameliorate insulin sensitivity, such as thiazolidinediones and metformin, are expected to improve or augment endothelial function in patients with diabetes. Glucagon-like peptide 1 receptor agonists, metformin, and sodium-glucose cotransporter 2 inhibitors may improve endothelial function through multiple mechanisms, some of which are independent of glucose control or insulin signaling. Oral administration of antioxidants is not recommended in patients with diabetes due to the lack of evidence for the efficacy against diabetic complications.

scholarly journals Oxidative Stress in Hypertensive Patients Induces an Increased Contractility in Vein Grafts Independent of Endothelial Function

2011 ◽  
Vol 2011 ◽  
pp. 1-8
Author(s):  
Claudio Joo Turoni ◽  
Rodrigo Marañón ◽  
Maria Karbiner ◽  
Juan Muntaner ◽  
Víctor Proto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Reactivity ◽  
Graft Patency ◽  
Hypertensive Patients ◽  
Antioxidant Agents ◽  
Diphenylene Iodonium ◽  
The Impact ◽  
Oxidative State

Objective. To evaluate the impact of oxidative stress on vascular reactivity to vasoconstrictors and on nitric oxide (NO) bioavailability in saphenous vein (SV) graft with endothelial dysfunction from hypertensive patients (HT).Methods. Endothelial function, vascular reactivity, oxidative state, nitrites and NO release were studied in isolated SV rings from HT and normotensive patients (NT). Only rings with endothelial dysfunction were used.Results. HT rings presented a hyperreactivity to vasoconstrictors that was reverted by diphenylene iodonium (DPI). In NT, no effect of DPI was obtained, but Nω-nitro-L-arginine methyl ester (L-NAME) increased the contractile response. NO was present in SV rings without endothelial function. Nitrites were higher in NT than in HT (1066.1 ± 86.3 pmol/mg;n=11versus 487.8 ± 51.6;n=23;P<0.01) and inhibited by nNOS inhibitor. L-arginine reversed this effect. Antioxidant agents increased nitrites and NO contents only in HT. The anti-nNOS-stained area by immunohistochemistry was higher in NT than HT. HT showed an elevation of oxidative state.Conclusions. Extraendothelial NO counter-regulates contractility in SV. However, this action could be altered in hypertensive situations by an increased oxidative stress or a decreased ability of nNOS to produce NO. Further studies should be performed to evaluate the implication of these results in graft patency rates.

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.

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.

scholarly journals VE-PTP inhibition elicits eNOS phosphorylation to blunt endothelial dysfunction and hypertension in diabetes

2020 ◽  
Author(s):  
Mauro Siragusa ◽  
Alberto Fernando Oliveira Justo ◽  
Pedro Felipe Malacarne ◽  
Anna Strano ◽  
Akshay Buch ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Dysfunction ◽  
Vascular Reactivity ◽  
Therapeutic Option ◽  
Diabetic Patients ◽  
No Production ◽  
Vascular Endothelial ◽  
Enos Activity

Abstract Aims Receptor-type vascular endothelial protein tyrosine phosphatase (VE-PTP) dephosphorylates Tie-2 as well as CD31, VE-cadherin, and vascular endothelial growth factor receptor 2 (VEGFR2). The latter form a signal transduction complex that mediates the endothelial cell response to shear stress, including the activation of the endothelial nitric oxide (NO) synthase (eNOS). As VE-PTP expression is increased in diabetes, we investigated the consequences of VE-PTP inhibition (using AKB-9778) on blood pressure in diabetic patients and the role of VE-PTP in the regulation of eNOS activity and vascular reactivity. Methods and results In diabetic patients AKB-9778 significantly lowered systolic and diastolic blood pressure. This could be linked to elevated NO production, as AKB increased NO generation by cultured endothelial cells and elicited the NOS inhibitor-sensitive relaxation of endothelium-intact rings of mouse aorta. At the molecular level, VE-PTP inhibition increased the phosphorylation of eNOS on Tyr81 and Ser1177 (human sequence). The PIEZO1 activator Yoda1, which was used to mimic the response to shear stress, also increased eNOS Tyr81 phosphorylation, an effect that was enhanced by VE-PTP inhibition. Two kinases, i.e. abelson-tyrosine protein kinase (ABL)1 and Src were identified as eNOS Tyr81 kinases as their inhibition and down-regulation significantly reduced the basal and Yoda1-induced tyrosine phosphorylation and activity of eNOS. VE-PTP, on the other hand, formed a complex with eNOS in endothelial cells and directly dephosphorylated eNOS Tyr81 in vitro. Finally, phosphorylation of eNOS on Tyr80 (murine sequence) was found to be reduced in diabetic mice and diabetes-induced endothelial dysfunction (isolated aortic rings) was blunted by VE-PTP inhibition. Conclusions VE-PTP inhibition enhances eNOS activity to improve endothelial function and decrease blood pressure indirectly, through the activation of Tie-2 and the CD31/VE-cadherin/VEGFR2 complex, and directly by dephosphorylating eNOS Tyr81. VE-PTP inhibition, therefore, represents an attractive novel therapeutic option for diabetes-induced endothelial dysfunction and hypertension.

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.

Sign in / Sign up

Export Citation Format

Share Document