Biochemistry and Basic Medical Sciences, Washington State University, 638 NE 41st Ave., Portland, OR 97232-3312, USA.
Int J Mol Sci. 2013 Nov 13;14(11):22274-330. doi: 10.3390/ijms141122274.
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 Ca(2+), 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.
NO/ONOO 循环是一种主要的局部生化恶性循环机制，以过氧亚硝酸盐和氧化应激为中心，但也涉及 10 个额外的元素：NF-κB、炎症细胞因子、iNOS、一氧化氮（NO）、超氧化物、线粒体功能障碍（降低能量电荷、ATP）、NMDA 活性、细胞内 Ca(2+)、TRP 受体和四氢生物蝶呤耗竭。这 12 个元素都在心力衰竭（HF）中起因果作用，每个元素都通过总共 87 项研究与 HF 的特定相关因素联系在一起。HF 的两个明显的因果因素，RhoA 和内皮素-1，每个因素都作为组织受限的循环元素起作用。有 19 种应激源会引发 HF 病例，每种应激源都会升高多个循环元素，从而以这种方式启动循环。不同类型的 HF，左心室与右心室 HF，伴或不伴心律失常等，在受循环影响最大的心肌区域可能彼此不同。循环的各个元素或连接它们的机制都不是原始的，但它们共同产生了强大的 NO/ONOO 循环性质，这给 HF 或其他拟议的 NO/ONOO 循环疾病的治疗带来了重大挑战。过氧亚硝酸盐/NO 比值升高和随之而来的氧化应激对 HF 和 NO/ONOO 循环都是必不可少的。
