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Int. J. Mol. Sci. 2013, 14(11), 22274-22330; doi:10.3390/ijms141122274
Review

The NO/ONOO-Cycle as the Central Cause of Heart Failure

Received: 29 June 2013; in revised form: 23 October 2013 / Accepted: 24 October 2013 / Published: 13 November 2013
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)
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Abstract: The NO/ONOO-cycle is a primarily local, biochemical vicious cycle mechanism, centered on elevated peroxynitrite and oxidative stress, but also involving 10 additional elements: NF-κB, inflammatory cytokines, iNOS, nitric oxide (NO), superoxide, mitochondrial dysfunction (lowered energy charge, ATP), NMDA activity, intracellular Ca2+, TRP receptors and tetrahydrobiopterin depletion. All 12 of these elements have causal roles in heart failure (HF) and each is linked through a total of 87 studies to specific correlates of HF. Two apparent causal factors of HF, RhoA and endothelin-1, each act as tissue-limited cycle elements. Nineteen stressors that initiate cases of HF, each act to raise multiple cycle elements, potentially initiating the cycle in this way. Different types of HF, left vs. right ventricular HF, with or without arrhythmia, etc., may differ from one another in the regions of the myocardium most impacted by the cycle. None of the elements of the cycle or the mechanisms linking them are original, but they collectively produce the robust nature of the NO/ONOO-cycle which creates a major challenge for treatment of HF or other proposed NO/ONOO-cycle diseases. Elevated peroxynitrite/NO ratio and consequent oxidative stress are essential to both HF and the NO/ONOO-cycle.
Keywords: nitrosative stress; reactive oxygen/nitrogen species; free radicals; inflammatory biochemistry; mitochondrial dysfunction; Ca2+ receptors; peroxynitrite; tetrahydrobiopterin oxidation nitrosative stress; reactive oxygen/nitrogen species; free radicals; inflammatory biochemistry; mitochondrial dysfunction; Ca2+ receptors; peroxynitrite; tetrahydrobiopterin oxidation
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Pall, M.L. The NO/ONOO-Cycle as the Central Cause of Heart Failure. Int. J. Mol. Sci. 2013, 14, 22274-22330.

AMA Style

Pall ML. The NO/ONOO-Cycle as the Central Cause of Heart Failure. International Journal of Molecular Sciences. 2013; 14(11):22274-22330.

Chicago/Turabian Style

Pall, Martin L. 2013. "The NO/ONOO-Cycle as the Central Cause of Heart Failure." Int. J. Mol. Sci. 14, no. 11: 22274-22330.



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