Department of Pharmacology, Faculty of Pharmacy, Beirut Arab University, Lebanon.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Egypt.
Eur J Pharmacol. 2014 Aug 15;737:210-3. doi: 10.1016/j.ejphar.2014.05.046. Epub 2014 Jun 2.
Since the discovery of the endothelin system in 1988, it has been implicated in numerous physiological and pathological phenomena. In the cardiovascular system, endothelin-1 (ET-1) acts through intracellular pathways of two endothelin receptors (ETA and ETB) located mainly on smooth muscle and endothelial cells to regulate vascular tone and provoke mitogenic and proinflammatory reactions. The endothelin ETA receptor is believed to play a pivotal role in the pathogenesis of several cardiovascular disease including systemic hypertension, pulmonary arterial hypertension (PAH), dilated cardiomyopathy, and diabetic microvascular dysfunction. Growing evidence from recent experimental and clinical studies indicates that the blockade of endothelin receptors, particularly the ETA subtype, grasps promise in the treatment of major cardiovascular pathologies. The simultaneous blockade of endothelin ETB receptors might not be advantageous, leading possibly to vasoconstriction and salt and water retentions. This review summarizes the role of ET-1 in cardiovascular modulation and the therapeutic potential of endothelin receptor antagonism.
自 1988 年发现内皮素系统以来，它已被牵涉到许多生理和病理现象中。在内皮素系统中，内皮素-1（ET-1）通过两种内皮素受体（ETA 和 ETB）的细胞内途径起作用，这些受体主要位于平滑肌和内皮细胞上，调节血管张力并引发有丝分裂和促炎反应。内皮素 ETA 受体被认为在几种心血管疾病的发病机制中发挥关键作用，包括全身性高血压、肺动脉高压（PAH）、扩张型心肌病和糖尿病微血管功能障碍。最近的实验和临床研究的大量证据表明，内皮素受体的阻断，特别是 ETA 亚型，在治疗主要心血管病变方面具有很大的前景。同时阻断内皮素 ETB 受体可能没有好处，可能导致血管收缩和盐和水潴留。这篇综述总结了 ET-1 在心血管调节中的作用和内皮素受体拮抗作用的治疗潜力。
