Rossi G P, Seccia T M, Nussdorfer G G
Department of Clinical and Experimental Medicine, University Hospital, University of Padua, Italy.
Int Rev Cytol. 2001;209:241-72. doi: 10.1016/s0074-7696(01)09014-3.
The endothelium plays a crucial role in the regulation of cardiovascular structure and function by releasing several mediators in response to biochemical and physical stimuli. These mediators are grouped into two classes: (1) endothelium-derived constricting factors (EDCFs) and (2) endothelium-derived relaxing factors (EDRFs), the roles of which are considered to be detrimental and beneficial, respectively. Endothelin-1 (ET-1) and nitric oxide (NO) are the prototypes of EDCFs and EDRFs, respectively, and their effects on the cardiovascular system have been studied in depth. Numerous conditions characterized by an impaired availability of NO have been found to be associated with enhanced synthesis of ET-1, and vice versa, thereby suggesting that these two factors have a reciprocal regulation. Experimental studies have provided evidence that ET-1 may exert a bidirectional effect by either enhancing NO production via ETB receptors located in endothelial cells or blunting it via ETA receptors prevalently located in the vascular smooth muscle cells. Conversely, NO was found to inhibit ET-1 synthesis in different cell types. In vitro and in vivo studies have started to unravel the molecular mechanisms involved in this complex interaction. It has been clarified that several factors affect in opposite directions the transcription of preproET-1 and NO-synthase genes, nuclear factor-KB and peroxisome proliferator-activated receptors playing a key role in these regulatory mechanisms. ET-1 and NO interplay seems to have a great relevance in the physiological regulation of vascular tone and blood pressure, as well as in vascular remodeling. Moreover, an imbalance between ET-1 and NO systems may underly the mechanisms involved in the pathogenesis of systemic and pulmonary hypertension and atherosclerosis.
内皮细胞通过对生化和物理刺激做出反应释放多种介质，在心血管结构和功能的调节中发挥关键作用。这些介质分为两类：（1）内皮源性收缩因子（EDCFs）和（2）内皮源性舒张因子（EDRFs），它们的作用分别被认为是有害的和有益的。内皮素-1（ET-1）和一氧化氮（NO）分别是EDCFs和EDRFs的典型代表，它们对心血管系统的影响已得到深入研究。已发现许多以NO可用性受损为特征的病症与ET-1合成增加有关，反之亦然，这表明这两种因子存在相互调节作用。实验研究提供了证据，表明ET-1可能通过位于内皮细胞的ETB受体增强NO生成，或通过主要位于血管平滑肌细胞的ETA受体使其减弱，从而发挥双向作用。相反，发现NO可抑制不同细胞类型中ET-1的合成。体外和体内研究已开始揭示这种复杂相互作用所涉及的分子机制。已经阐明，几种因素以相反方向影响前体ET-1和NO合酶基因的转录，核因子-κB和过氧化物酶体增殖物激活受体在这些调节机制中起关键作用。ET-1与NO的相互作用似乎在血管张力和血压的生理调节以及血管重塑中具有重要意义。此外，ET-1和NO系统之间的失衡可能是系统性和肺动脉高压以及动脉粥样硬化发病机制所涉及的基础。
