Nitroso-redox balance in the cardiovascular system.

  title={Nitroso-redox balance in the cardiovascular system.},
  author={Joshua M. Hare},
  journal={The New England journal of medicine},
  volume={351 20},
  • J. Hare
  • Published 11 November 2004
  • Medicine
  • The New England journal of medicine
In this issue of the Journal, Taylor and colleagues report the results of the African-American Heart Failure Trial (A-HeFT), a double-blind, randomized trial that evaluated the effect of the addition of isosorbide dinitrate and hydralazine to the best conventional therapy in patients with symptomatic congestive heart failure who identified themselves as black.1 The results with the combination therapy were markedly positive, meeting the composite end point of the trial, which included death… 

Figures from this paper

Nitroso-redox imbalance affects cardiac structure and function.

Hydralazine and Isosorbide Dinitrate in Heart Failure: Historical Perspective, Mechanisms, and Future Directions

Until the 1970s, treatment options for heart failure were limited to digitalis and diuretics, and the search for more effective options led to strategies that modulated hemodynamics, which led to studies with oral agents, including hydralazine, isosorbide dinitrate (ISDN), prazosin, phentolamine, and minoxidil.

Reassessing the use of vasodilators in heart failure

Clinical trials of vasodilators in the treatment of heart failure have resulted in either neutral or negative outcomes suggesting that systemic vascular resistance may be an inappropriate target of therapy, and future studies of vasODilators will need to consider these issues in trial design.

Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure Patients: Design and Rationale of the EXACT-HF Study

Evidence supports the hypothesis that HF is associated with an increase in the activity of XO, which, in turn, increases production of superoxide and uric acid during purine metabolism, which may be exacerbated by decreased activity of nitric oxide synthase.

Isosorbide dinitrate-hydralazine combination therapy in African Americans with heart failure

The addition of ISDN-HYD, vasodilator therapy that enhances nitric oxide and reduces oxidative stress, further improves quality of life and survival in African American patients with heart failure.

Fixed combination isosorbide dinitrate–hydralazine for nitric-oxide-enhancing therapy in heart failure

The recently reported beneficial effects of the fixed combination of isosorbide dinitrate and hydralazine (ISDN+HYD) in the African-American Heart Failure Trial (A-HeFT), has led to both the FDA approval of this agent and its endorsement by the latest HF guidelines.

Endothelial dysfunction in heart failure and ischemic heart disease: rationale for the clinical use of mononitrates

In the light of the important role of oxidative stress in the progression of heart failure, reduced occupation of the receptors for NO by IS-2-MN could have important implications for the bioavailability of the sulphydryl groups otherwise involved in the denitrification of the organic molecules.

BiDil (isosorbide dinitrate and hydralazine): a new fixed-dose combination of two older medications for the treatment of heart failure in black patients.

Current evidence-based treatment guidelines recommend that the addition of ISDN and hydralazine in black patients with moderate to severe HF optimized on standard therapy be considered, and BiDil is currently indicated for the treatment of HF as an adjunct to standard therapy inblack patients.

Combination of isosorbide dinitrate and hydralazine in blacks with heart failure.

The addition of a fixed dose of isosorbide dinitrate plus hydralazine to standard therapy for heart failure including neurohormonal blockers is efficacious and increases survival among black patients with advanced heart failure.

A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure.

The different effects of the two regimens (enalapril and hydralazine-isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination.

Allopurinol Improves Myocardial Efficiency in Patients With Idiopathic Dilated Cardiomyopathy

By reversing the energetic inefficiency of the failing heart, pharmacological XO inhibition represents a potential novel therapeutic strategy for the treatment of human heart failure.

Hydralazine prevents nitroglycerin tolerance by inhibiting activation of a membrane-bound NADH oxidase. A new action for an old drug.

The ability of hydralazine to inhibit vascular .O2- anion production represents a novel mechanism of action for this drug.

Red Blood Cell Nitric Oxide as an Endocrine Vasoregulator: A Potential Role in Congestive Heart Failure

It is confirmed that RBC-bound NO mediates hypoxic vasodilation in vitro and in vivo in healthy subjects and patients with congestive heart failure (CHF), and transpulmonary gradients of hemoglobin-boundNO are evident in CHF patients and are inversely dependent on cardiac index.

Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications

XOR gene structure and regulation, protein structure, enzymology, tissue distribution and pathophysiological role in cardiovascular disease with an emphasis on heart failure are reviewed.

Central role of mitochondrial aldehyde dehydrogenase and reactive oxygen species in nitroglycerin tolerance and cross-tolerance.

Nitrate tolerance is mediated, at least in significant part, by inhibition of vascular ALDH-2 and that mitochondrial ROS contribute to this inhibition, and GTN tolerance may be viewed as a metabolic syndrome characterized by mitochondrial dysfunction.

Neuronal nitric oxide synthase negatively regulates xanthine oxidoreductase inhibition of cardiac excitation-contraction coupling.

  • S. KhanKwangho Lee J. Hare
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2004
It is demonstrated that xanthine oxidoreductase (XOR), a prototypic superoxide O(2)(.-) -producing enzyme, and neuronal nitric oxide synthase (NOS1) coimmunoprecipitate and colocalize in the sarcoplasmic reticulum of cardiac myocytes.

Activation of the cardiac calcium release channel (ryanodine receptor) by poly-S-nitrosylation.

Results reveal that ion channels can differentiate nitrosative from oxidative signals and indicate that the cardiac calcium release channel (ryanodine receptor) in canines is regulated by posttranslational chemical modification(s) of sulfurs.