Role of nitric oxide and oxidative stress in baroreceptor dysfunction in patients with chronic heart failure

2003 ◽  
Vol 104 (5) ◽  
pp. 529-535 ◽  
Author(s):  
Angus K. NIGHTINGALE ◽  
Daniel J. BLACKMAN ◽  
Rachel FIELD ◽  
Natalie J. GLOVER ◽  
Nicholas PEGGE ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Vitamin C ◽  
Radical Scavenging ◽  
Oral Vitamin ◽  
Baroreflex Control ◽  
Age Related ◽  
Intravenous Vitamin ◽  
To Receive

Abnormalities of autonomic control of the cardiovascular system are seen in chronic heart failure (CHF) and confer a poor prognosis. Nitric oxide appears to be important in the regulation of baroreflex control in health and in disease states. The antioxidant vitamin C increases nitric oxide bioavailability in CHF. We evaluated the effects of vitamin C on baroreceptor sensitivity (BRS) by sequence analysis in 100 CHF patients and 44 control subjects. Groups of 55 CHF patients and 22 controls were randomly allocated to receive a single intravenous injection of vitamin C (2 g) or placebo. In addition, 45 CHF patients were randomly allocated to receive a 4-week course of oral vitamin C (4 g/day) or placebo. An age-related reference range for BRS was developed in 22 healthy controls matched for age and gender to the CHF group. BRS was significantly impaired in the CHF group compared with age-matched older controls and young controls (6.9 ± 3.1, 12.5 ± 4.9 and 21.7 ± 9.1 mmHg/ms respectively; P < 0.001 between groups). Intravenous vitamin C acutely improved BRS in CHF patients by 24% (by 1.8 ± 4.1 mmHg/ms; P < 0.05), but not in controls. There was no improvement in BRS in CHF patients given chronic oral vitamin C. Thus acute intravenous, but not chronic oral, vitamin C improved BRS in CHF patients. There was no effect of intravenous vitamin C in healthy subjects, suggesting that the mechanism was either by free radical scavenging or due to central effects.

scholarly journals Despite improving endothelial function oral vitamin C increases phosphocreatine depletion during exercise in patients with chronic heart failure

2002 ◽  
Vol 39 ◽  
pp. 182
Author(s):  
Angus K. Nightingale ◽  
Jenny G. Crilley ◽  
Nicholas C. Pegge ◽  
Rachel C. Field ◽  
Matthias Schmitt ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Vitamin C ◽  
Endothelial Function ◽  
Oral Vitamin

Acute Effects of Vitamin C on Platelet Responsiveness to Nitric Oxide Donors and Endothelial Function in Patients with Chronic Heart Failure

2001 ◽  
Vol 37 (5) ◽  
pp. 564-570 ◽  
Author(s):  
Gethin R. Ellis ◽  
Richard A. Anderson ◽  
Yuliy Y. Chirkov ◽  
Jayne Morris-Thurgood ◽  
Simon K. Jackson ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Vitamin C ◽  
Endothelial Function ◽  
Nitric Oxide Donors ◽  
Acute Effects

scholarly journals Effect of frailty on treatment, hospitalisation and death in patients with chronic heart failure

2021 ◽  
Author(s):  
S. Sze ◽  
P. Pellicori ◽  
J. Zhang ◽  
J. Weston ◽  
I. B. Squire ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Clinical Frailty Scale ◽  
Mineralocorticoid Receptor Antagonist ◽  
Reduced Ejection Fraction ◽  
Frail Patients ◽  
History Of ◽  
Poor Outcomes ◽  
To Receive

Abstract Background Frailty is common in patients with chronic heart failure (CHF) and is associated with poor outcomes. The natural history of frail patients with CHF is unknown. Methods Frailty was assessed using the clinical frailty scale (CFS) in 467 consecutive patients with CHF (67% male, median age 76 years, median NT-proBNP 1156 ng/L) attending a routine follow-up visit. Those with CFS > 4 were classified as frail. We investigated the relation between frailty and treatments, hospitalisation and death in patients with CHF. Results 206 patients (44%) were frail. Of 291 patients with HF with reduced ejection fraction (HeFREF), those who were frail (N = 117; 40%) were less likely to receive optimal treatment, with many not receiving a renin–angiotensin–aldosterone system inhibitor (frail: 25% vs. non-frail: 4%), a beta-blocker (16% vs. 8%) or a mineralocorticoid receptor antagonist (50% vs 41%). By 1 year, there were 56 deaths and 322 hospitalisations, of which 25 (45%) and 198 (61%), respectively, were due to non-cardiovascular (non-CV) causes. Most deaths (N = 46, 82%) and hospitalisations (N = 215, 67%) occurred in frail patients. Amongst frail patients, 43% of deaths and 64% of hospitalisations were for non-CV causes; 58% of cardiovascular (CV) deaths were due to advancing HF. Among non-frail patients, 50% of deaths and 57% of hospitalisations were for non-CV causes; all CV deaths were due to advancing HF. Conclusion Frailty in patients with HeFREF is associated with sub-optimal medical treatment. Frail patients are more likely to die or be admitted to hospital, but whether frail or not, many events are non-CV. Graphical abstract

scholarly journals Airway and cough responsiveness and exhaled nitric oxide in non-smoking patients with stable chronic heart failure.

Heart ◽  
1996 ◽  
Vol 76 (2) ◽  
pp. 144-149 ◽  
Author(s):  
T. P. Chua ◽  
U. G. Lalloo ◽  
M. Y. Worsdell ◽  
S. Kharitonov ◽  
K. F. Chung ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Exhaled Nitric Oxide

Abstract 15532: Altered Ubiquitination and Stability of Protein Inhibitor of Neuronal Nitric Oxide Synthase in the Paraventricular Nucleus of Chronic Heart Failure Rats: Role of Angiotensin II

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Neeru Sharma ◽  
Xuefei Liu ◽  
Hong Zheng ◽  
Kaushik Patel
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Angiotensin Ii ◽  
Chronic Heart Failure ◽  
Paraventricular Nucleus ◽  
Neuronal Nitric Oxide Synthase ◽  
Ang Ii ◽  
Protein Inhibitor ◽  
Ubiquitin Proteasome ◽  
Oxide Synthase

Introduction and Hypothesis: Expression of neuronal nitric oxide synthase (nNOS) is decreased in the paraventricular nucleus (PVN) of rats with chronic heart failure (CHF), however the underlying molecular mechanism/s remain unclear. Recently, we demonstrated, Angiotensin II (Ang II) mediated increase in PIN: protein inhibitor of nNOS (0.76±0.10 Sham vs 1.12±0.09* CHF) which is known to down-regulate nNOS through disruption of active dimers (~60% decrease in dimer/monomer ratio) in the PVN of rats with CHF. Functionally impeded monomeric enzyme is degraded by ubiquitin proteasome system. Interestingly, PIN transcript levels remain unchanged in the PVN in CHF (1.00±0.23 Sham vs. 1.1±0.28 CHF). This observation prompted us to elucidate the molecular mechanism for the accumulation of PIN post-transcriptionally in the PVN in CHF Methods and Results: We used coronary artery ligation model of CHF in rats (6-8 weeks past ligation) and neuronal NG108-15 hybrid cell line. PIN translation was inhibited using cyclohexamide (CHX) for 0-4h after 20h of pretreatment with Ang II in NG108 cells. CHX mediated decrease in PIN expression was ameliorated with Ang II (0.19±0.04 vs 0.41±0.06* 4h). Proteasome inhibitor lactacystin (LC) treatment dramatically elevates PIN level suggesting the involvement of proteasome system in PIN regulation. Immunoprecipitation with ubiquitin antibody showed decrease PIN-Ub conjugates in Ang II-treated cells (1.04 ± 0.05 LC vs. 0.62 ± 0.07* LC AngII). In vitro ubiquitination assay in cells transfected with pCMV-(HA-Ub)8 vector revealed reduction of HA-Ub-PIN conjugates after Ang II treatment (9.2 ± 2.2 LC vs. 4.5 ± 0.6* LC Ang II). Furthermore, there was decreased accumulation of PIN-Ub conjugates in the PVN of CHF rats compared to Sham as revealed by immunohistochemistry. Conclusions: Taken together, our studies revealed that PIN is targeted for rapid degradation by the ubiquitin-proteasome pathway and Ang II delays the rate of degradation resulting in accumulation of PIN. We conclude that post-translational accumulation of PIN, mediated by Ang II, leads to a decrease in the dimeric active form of nNOS as well as protein levels of nNOS, which may lead to reduced nitric oxide resulting in over-activation of sympathetic drive during CHF.

scholarly journals Vitamin C—An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3760 ◽  
Author(s):  
Patrick Holford ◽  
Anitra C. Carr ◽  
Thomas H. Jovic ◽  
Stephen R. Ali ◽  
Iain S. Whitaker ◽  
...  
Keyword(s):  
Vitamin C ◽  
Adjunctive Therapy ◽  
Respiratory Infections ◽  
Low Cost ◽  
Oral Vitamin ◽  
Vitamin C Deficiency ◽  
Favourable Safety ◽  
Favourable Safety Profile ◽  
Hospital Stays ◽  
Intravenous Vitamin

There are limited proven therapies for COVID-19. Vitamin C’s antioxidant, anti-inflammatory and immunomodulating effects make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19. This literature review focuses on vitamin C deficiency in respiratory infections, including COVID-19, and the mechanisms of action in infectious disease, including support of the stress response, its role in preventing and treating colds and pneumonia, and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2–8 g/day) may reduce the incidence and duration of respiratory infections and intravenous vitamin C (6–24 g/day) has been shown to reduce mortality, intensive care unit (ICU) and hospital stays, and time on mechanical ventilation for severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and the frequency of vitamin C deficiency in respiratory infections, it may be worthwhile testing patients’ vitamin C status and treating them accordingly with intravenous administration within ICUs and oral administration in hospitalised persons with COVID-19.

Pharmacotherapy of Chronic Heart Failure in the Elderly: A Review of the Evidence

2010 ◽  
Vol 2 ◽  
pp. CMT.S2794
Author(s):  
Toni L. Ripley ◽  
Thomas A. Hennebry
Keyword(s):  
Heart Failure ◽  
Clinical Trials ◽  
Older Patients ◽  
The Elderly ◽  
The United States ◽  
Response To Therapy ◽  
Clinical Endpoints ◽  
Age Related ◽  
Prevalent Disease ◽  
To Receive

Heart failure (HF) is a very prevalent disease in the United States and in Europe, with the highest prevalence among older patients. Population estimates suggest substantial growth among the elderly over the next four decades. However, older patients are underrepresented in clinical trials evaluating HF therapies and are less likely to receive the medications shown in these trials to reduce the morbidity and mortality associated with HF. Age-related differences exist in cardiovascular function that may affect disease progression, clinical presentation, and/or response to therapy. Further, medication use in older patients is complicated by physiologic changes in pharmacokinetics and the presence of multiple co-morbidities, which leads to polypharmacy and the related complications. We reviewed the pharmacotherapy clinical trials in HF to review the results specifically in older patients. Trials were included in this review if clinical endpoints were evaluated, if data regarding the participants’ age was reported, and if the intervention studied was in a medication class that is generally recommended for patients with HF by published guidelines. Although some non-randomized data shows benefits of standard therapies may be maintained among patients with HF ≥ 60 years old, the randomized controlled trials that have been published to date showed no benefit and no harm in this group. Cautious HF management among older patients is critical as additional evidence is pursued.

Sign in / Sign up

Export Citation Format

Share Document