Conflicting effects of nitric oxide and oxidative stress in chronic heart failure: potential therapeutic strategies

Abstract

Chronic heart failure (CHF) is characterized by decreased nitric oxide (NO) bioavailability. In addition, the beneficial NO turns to be deleterious when it reacts with superoxide anion, leading to peroxynitrite formation. Numerous experimental and clinical studies have reported increased production of reactive oxygen species (superoxide, hydrogen peroxide, hydroxyl radical) both in animals and patients with CHF. Moreover, there are indicative data suggesting mechanisms associated with endothelial dysfunction in states of CHF, mainly attributed to decreased NO bioavailability and enhanced inactivation of the latter. Thus, such molecules appear to be potential targets in patients with CHF. These patients are strong candidates to receive a variety of therapeutic agents, some of which have known antioxidant effects. Classic treatment with statins or angiotensin converting enzyme inhibitors has been found to be beneficial in restoring NO and improving myocardial function and structure. Other agents such as sildenafil and b-blockers along with novel agents such as NO synthase transcription enhancers have been proved to be also beneficial, but their use for such a purpose is still controversial. Approaches using more-effective antioxidants or targeting myocardial oxidant-producing enzymes and oxidative or nitrosative stress might be promising strategies in the future.

Increased NT-proANP predicts risk of congestive heart failure in Cavalier King Charles spaniels with mitral regurgitation caused by myxomatous valve disease

“…On the other hand, with maintained endothelial function, NO in combination with the natriuretic peptides is an important beneficial counter-regulatory factor. 43 Therefore, the decreased hazard with increase in initial NOx concentrations could indicate that dogs in our study initially had normal endothelial function and could increase their endothelial NO production to maintain peripheral blood flow. This explanation seems plausible, because mean age at enrollment was 6.6 AE 2.1 years, whereas arteriosclerotic changes reported in necropsy material are from older animals (median 11 years).…”

“…endothelial dysfunction, is an important cardiovascular risk factor. 43,44 Unfortunately plasma NOx levels are influenced by gastrointestinal sources (digested protein, bacterial source, vegetable NOx content, etc.). Although blood samples were taken from fasted animals, we cannot exclude the possibility that some animals could have ingested food, thus contributing to the high variability in plasma NOx concentrations compared to NTproANP.…”

MicroRNAs in Cardiovascular Disease

“…It is accompanied by complex molecular mechanisms and neurovascular activation, and structural and functional abnormalities which are responsible for high mortality and morbidity. 30,160 Clinical studies have demonstrated that miRNA profiles of human hearts with heart failure compared with hearts of healthy individuals differ between these 2 groups. 125 In this model, several miRNAs have been found to alter their expression patterns providing diagnostic charge so as to distinguish between ischemic and nonischemic heart failure.…”

Pentaerythritol Tetranitrate Targeting Myocardial Reactive Oxygen Species Production Improves Left Ventricular Remodeling and Function in Rats With Ischemic Heart Failure

“…Thereby, NO is rapidly oxidized by superoxide anions to peroxynitrite, contributing to nitrosative stress ultimately leading to myocardial and vascular dysfunction. 1,25,26 Common organic nitrates release NO, but a pharmacological approach solely built on the concept of releasing NO bares the risk of being ineffective. Furthermore, development of nitrate tolerance and the induction of superoxide anion production limits their long-term use in heart failure.…”