Pechánová O, Simko F
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Physiol Res. 2007;56 Suppl 2:S7-S16. doi: 10.33549/physiolres.931392. Epub 2007 Sep 5.
Endothelial dysfunction may be considered as the interstage between risk factors and cardiovascular pathology. An imbalance between the production of vasorelaxing and vasoconstricting factors plays a decisive role in the development of hypertension, atherosclerosis and target organ damage. Except vasorelaxing and antiproliferative properties per se, nitric oxide participates in antagonizing vasoconstrictive and growth promoting effects of angiotensin II, endothelins and reactive oxygen species. Angiotensin II is a potent activator of NAD(P)H oxidase contributing to the production of reactive oxygen species. Numerous signaling pathways activated in response to angiotensin II and endothelin-1 are mediated through the increased level of oxidative stress, which seems to be in casual relation to a number of cardiovascular disturbances including hypertension. With respect to the oxidative stress, the NO molecule seems to be of ambivalent nature. On the one hand, NO is able to reduce generation of reactive oxygen species by inhibiting association of NAD(P)H oxidase subunits. On the other hand, when excessively produced, NO reacts with superoxides resulting in the formation of peroxynitrite, which is a free radical deteriorating endothelial function. The balance between vasorelaxing and vasoconstricting substances appears to be the principal issue for the physiological functioning of the vascular bed.
内皮功能障碍可被视为风险因素与心血管病变之间的中间阶段。血管舒张因子和血管收缩因子生成之间的失衡在高血压、动脉粥样硬化和靶器官损害的发展中起决定性作用。除了其本身的血管舒张和抗增殖特性外，一氧化氮还参与拮抗血管紧张素II、内皮素和活性氧的血管收缩和促生长作用。血管紧张素II是NAD(P)H氧化酶的有效激活剂，有助于活性氧的产生。响应血管紧张素II和内皮素-1而激活的众多信号通路是通过氧化应激水平的升高介导的，氧化应激似乎与包括高血压在内的许多心血管紊乱存在因果关系。就氧化应激而言，NO分子似乎具有矛盾的性质。一方面，NO能够通过抑制NAD(P)H氧化酶亚基的结合来减少活性氧的产生。另一方面，当NO过度产生时，它会与超氧化物反应生成过氧亚硝酸盐，过氧亚硝酸盐是一种使内皮功能恶化的自由基。血管舒张物质和血管收缩物质之间的平衡似乎是血管床生理功能的主要问题。
