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.

Abstract P097: Angiotensin Receptor Neprilysin Inhibition Improves Arterial Stiffness And Endothelial Function In Heart Failure With Reduced Ejection Fraction

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Sangeetha D Nathaniel ◽  
Shane McGinty ◽  
David G Edwards ◽  
William B Farquhar ◽  
Melissa A Witman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Arterial Stiffness ◽  
Ejection Fraction ◽  
Endothelial Function ◽  
Repeated Measures ◽  
Vascular Function ◽  
Nyha Class ◽  
Angiotensin Receptor ◽  
Reduced Ejection Fraction ◽  
Neprilysin Inhibitor

The mechanisms for the benefits of Angiotensin Receptor Neprilysin inhibitor (ARNi) in heart failure patients with reduced ejection fraction (HFrEF) are likely beyond blood pressure (BP) reduction. Vascular function, a prognostic marker in HFrEF, improves with ARNi in animal models. Improvements in vascular function may contribute to benefits from ARNi in HFrEF; however, this has yet to be demonstrated in humans. The purpose of the study was to test the hypothesis that arterial stiffness and endothelial function would improve after 12 weeks of ARNi in HFrEF. Methods: HFrEF participants with NYHA class II-III were enrolled from local cardiology clinics and completed experimental visits at baseline and 12 weeks later: 13 participants were prescribed ARNi by their cardiologist [62±10 years, Men: 10, BMI: 30±5 kg/m 2 , EF: 28±6 %; Non-ischemic cardiomyopathy (NICM): 8], 10 participants continued on conventional treatment [CON: 60±7 years, Men: 6, BMI: 31±6 kg/m 2 , EF: 31±5 % and NICM: 4; all P=NS]. During each experimental visit, arterial stiffness was assessed via carotid-femoral pulse wave velocity (PWV; Sphygmocor PVx system) and endothelial function by brachial artery flow-mediated dilation (FMD) using standard techniques. Statistical analyses were performed using 2x2 repeated-measures ANOVA. Results: Baseline mean BP (MAP) was similar between ARNi (93±14 mmHg) and CON (85 ± 10 mmHg; P=0.13); MAP tended to decrease after 12 weeks of ARNi (88 ± 11 mmHg; P=0.08) but not CON (90 ± 17 mmHg; P=0.14) (ANOVA interaction P=0.03). PWV tended to be higher at baseline in ARNi (8.8 ± 2.5 m/s) compared to CON (7.0 ± 2.5 m/s; P=0.09); PWV decreased after 12 weeks of ARNi (7.0 ± 1.7 m/s; P<0.01) and was unchanged in CON (7.4 ± 2.4 m/s; P=0.33) (ANOVA interaction P<0.01). When controlling for MAP, the effect of ARNi on PWV remained (P<0.01). At baseline, FMD was similar between ARNi (2.81 ± 2.05%) and CON (4.75 ± 3.75%; P=0.13); however, FMD increased after 12 weeks of ARNi (5.73 ± 1.87%; P<0.001) but not in CON (5.37 ± 3.38%; P=0.33) (ANOVA time P<0.001, interaction P=0.01). Conclusion: ARNi improves arterial stiffness and endothelial function in HFrEF. Understanding the mechanisms of ARNi in HFrEF is crucial as it may pave the way for better interventions in other cardiovascular diseases.

scholarly journals Preservation of venous endothelial function in the forearm venous capacitance bed of patients with chronic heart failure despite arterial endothelial dysfunction

2001 ◽  
Vol 37 (4) ◽  
pp. 1062-1068 ◽  
Author(s):  
Angus K Nightingale ◽  
Daniel J Blackman ◽  
Gethin R Ellis ◽  
Matthias Schmitt ◽  
Jayne A Morris-Thurgood ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Venous Capacitance

scholarly journals Acute impact of conventional and eccentric cycling on platelet and vascular function in patients with chronic heart failure

2017 ◽  
Vol 122 (6) ◽  
pp. 1418-1424 ◽  
Author(s):  
Andrew Haynes ◽  
Matthew D. Linden ◽  
Lauren C. Chasland ◽  
Kazunori Nosaka ◽  
Andrew Maiorana ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Platelet Function ◽  
Vascular Function ◽  
Acute Exercise ◽  
Moderate Intensity ◽  
Reduced Ejection Fraction ◽  
Exercise Modality ◽  
Flow Cytometric ◽  
Evidence Based Guidelines

Evidence-based guidelines recommend exercise therapy for patients with chronic heart failure (CHF). Such patients have increased atherothrombotic risk. Exercise can transiently increase platelet activation and reactivity and decrease vascular function in healthy participants, although data in CHF are scant. Eccentric (ECC) cycling is a novel exercise modality that may be particularly suited to patients with CHF, but the acute impacts of ECC cycling on platelet and vascular function are currently unknown. Our null hypothesis was that ECC and concentric (CON) cycling, performed at matched external workloads, would not induce changes in platelet or vascular function in patients with CHF. Eleven patients with heart failure with reduced ejection fraction (HFrEF) took part in discrete bouts of ECC and CON cycling. Before and immediately after exercise, vascular function was assessed by measuring diameter and flow-mediated dilation (FMD) of the brachial artery. Platelet function was measured by the flow cytometric determination of glycoprotein IIb/IIIa activation and granule exocytosis in the presence and absence of platelet agonists. ECC cycling increased baseline artery diameter (pre: 4.0 ± 0.8 mm vs. post: 4.2 ± 0.7 mm; P = 0.04) and decreased FMD%. When changes in baseline artery diameter were accounted for, the decrease in FMD post-ECC cycling was no longer significant. No changes were apparent after CON. Neither ECC nor CON cycling resulted in changes to any platelet-function measures (all P > 0.05). These results suggest that both ECC and CON cycling, at a moderate intensity and short duration, can be performed by patients with HFrEF without detrimental impacts on vascular or platelet function. NEW & NOTEWORTHY This is the first evidence to indicate that eccentric (ECC) cycling can be performed relatively safely by patients with chronic heart failure (CHF), as it did not result in impaired vascular or platelet function compared with conventional cycling. This is important, as acute exercise can transiently increase atherothrombotic risk, and ECC cycling is a novel exercise modality that may be particularly suited to patients with CHF.

scholarly journals Vascular Oxidative Stress and Endothelial Dysfunction in Patients With Chronic Heart Failure

Circulation ◽  
2002 ◽  
Vol 106 (24) ◽  
pp. 3073-3078 ◽  
Author(s):  
Ulf Landmesser ◽  
Stephan Spiekermann ◽  
Sergey Dikalov ◽  
Helma Tatge ◽  
Ragna Wilke ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Endothelial Dysfunction ◽  
Vascular Oxidative Stress

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.

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.

Sign in / Sign up

Export Citation Format

Share Document