Bruno Rosa Maria, Masi Stefano, Taddei Marco, Taddei Stefano, Virdis Agostino
Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56100, Pisa, Italy.
Department of Emergency, University Hospital of Pisa, Pisa, Italy.
High Blood Press Cardiovasc Prev. 2018 Mar;25(1):35-40. doi: 10.1007/s40292-017-0245-9. Epub 2018 Jan 9.
In healthy conditions, the endothelium plays a pivotal role in maintaining vascular homeostasis, mainly by the production of the relaxing factor nitric oxide (NO), which protects the vessel wall from those mechanisms favouring the development of vascular atherosclerosis. Aging is a powerful cardiovascular risk factors associated with endothelial dysfunction. In details, an alteration in the NO substrate L-arginine is the major factor responsible for endothelial dysfunction with advancing age, while reactive oxygen species (ROS) excess generation, which in turn reduce NO availability, plays a role in oldest individuals only. NO inhibition by ROS excess is the main cause of endothelial dysfunction which occurs in many other clinical conditions including arterial hypertension. Although hypertension induces early vascular aging in several arterial districts, however vascular features of physiological aging and hypertension are not necessarily similar. While an impaired NO availability represents the common final effect, aging and hypertension seem to adopt different mechanisms, at least at the level of microcirculation. Indeed, physiological aging shows a progressive reduced NO availability, while in advanced age some degree of oxidative stress emerges. In hypertensive patients, NO availability is early reduced, but the progression rate with age appears to be similar. Whether the hypertensive- and age-related vascular alterations represent only a mere additive effect of two independent risk factors resulting in endothelial dysfunction awaits further clarification.
在健康状态下，内皮主要通过产生舒张因子一氧化氮（NO）在维持血管稳态中发挥关键作用，NO可保护血管壁免受那些促进血管动脉粥样硬化发展的机制影响。衰老为与内皮功能障碍相关的一个强大心血管危险因素。具体而言，随着年龄增长，NO底物L-精氨酸的改变是导致内皮功能障碍的主要因素，而活性氧（ROS）生成过多，进而降低NO的可用性，仅在老年人中起作用。ROS生成过多导致的NO抑制是包括动脉高血压在内的许多其他临床病症中发生内皮功能障碍的主要原因。虽然高血压在多个动脉区域诱发早期血管衰老，然而生理衰老和高血压的血管特征不一定相似。虽然NO可用性受损代表共同的最终效应，但衰老和高血压似乎采用不同机制，至少在微循环水平如此。的确，生理衰老表现为NO可用性逐渐降低，而在高龄时会出现一定程度的氧化应激。在高血压患者中，NO可用性早期降低，但随年龄的进展速率似乎相似。高血压和年龄相关的血管改变是否仅代表导致内皮功能障碍的两个独立危险因素的单纯相加效应，有待进一步阐明。
