Coffey M J, Coles B, O'Donnell V B
Wales Heart Research Institute, University of Wales College of Medicine, Heath Park, Cardiff, Wales CF14 4XN, United Kingdom.
Free Radic Res. 2001 Nov;35(5):447-64. doi: 10.1080/10715760100301471.
Nitric oxide (NO) is a major free radical modulator of smooth muscle tone, which under basal conditions acts to preserve vascular homeostasis through its anti-inflammatory properties. The biochemistry of NO, in particular, its rapid conversion in vivo into secondary reactive nitrogen species (RNS), its chemical nature as a free radical and its high diffusibility and hydrophobicity dictate that this species will interact with numerous biomolecules and enzymes. In this review, we consider the interactions of a number of enzymes found in the vasculature with NO and NO-derived RNS. All these enzymes are either homeostatic or promote the development of atherosclerosis and hypertension. Therefore their interactions with NO and NO-derived RNS will be of central importance in the initiation and progression of vascular disease. In some examples, (e.g. lipoxygenase, LOX), such interactions provide catalytic 'sinks' for NO, but for others, in particular peroxidases and prostaglandin H synthase (PGHS), reactions with NO may be detrimental. Nitric oxide and NO-derived RNS directly modulate the activity of vascular peroxidases and LOXs through a combination of effects, including transcriptional regulation, altering substrate availability, and direct reaction with enzyme turnover intermediates. Therefore, these interactions will have two major consequences: (i) depletion of NO levels available to cause vasorelaxation and prevent leukocyte/platelet adhesion and (ii) modulation of activity of the target enzymes, thereby altering the generation of bioactive signaling molecules involved in maintenance of vascular homeostasis, including prostaglandins and leukotrienes.
一氧化氮（NO）是平滑肌张力的主要自由基调节剂，在基础条件下，它通过其抗炎特性来维持血管稳态。NO的生物化学性质，特别是它在体内迅速转化为次级反应性氮物种（RNS），其作为自由基的化学性质以及高扩散性和疏水性，决定了该物质会与众多生物分子和酶相互作用。在本综述中，我们考虑了血管系统中发现的多种酶与NO及NO衍生的RNS之间的相互作用。所有这些酶要么具有稳态功能，要么促进动脉粥样硬化和高血压的发展。因此，它们与NO及NO衍生的RNS的相互作用在血管疾病的发生和发展中至关重要。在一些例子中（如脂氧合酶，LOX），这种相互作用为NO提供了催化“汇”，但对于其他酶，特别是过氧化物酶和前列腺素H合酶（PGHS），与NO的反应可能是有害的。一氧化氮和NO衍生的RNS通过多种效应的组合直接调节血管过氧化物酶和LOX的活性，这些效应包括转录调控、改变底物可用性以及与酶周转中间体的直接反应。因此，这些相互作用将产生两个主要后果：（i）可用于引起血管舒张并防止白细胞/血小板粘附的NO水平降低；（ii）调节靶酶的活性，从而改变参与维持血管稳态的生物活性信号分子的生成，包括前列腺素和白三烯。
