Kedzierski R M, Yanagisawa M
Department of Molecular Genetics University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9050, USA.
Annu Rev Pharmacol Toxicol. 2001;41:851-76. doi: 10.1146/annurev.pharmtox.41.1.851.
The endothelin system consists of two G-protein-coupled receptors, three peptide ligands, and two activating peptidases. Its pharmacological complexity is reflected by the diverse expression pattern of endothelin system components, which have a variety of physiological and pathophysiological roles. In the vessels, the endothelin system has a basal vasoconstricting role and participates in the development of diseases such as hypertension, atherosclerosis, and vasospasm after subarachnoid hemorrhage. In the heart, the endothelin system affects inotropy and chronotropy, and it mediates cardiac hypertrophy and remodeling in congestive heart failure. In the lungs, the endothelin system regulates the tone of airways and blood vessels, and it is involved in the development of pulmonary hypertension. In the kidney, it controls water and sodium excretion and acid-base balance, and it participates in acute and chronic renal failure. In the brain, the endothelin system modulates cardiorespiratory centers and the release of hormones. More advanced functional analysis of the endothelin system awaits not only additional pharmacological studies using highly specific endothelin antagonists but also the generation of genetically altered rodent models with conditional loss-of-function and gain-of-function manipulations.
内皮素系统由两种G蛋白偶联受体、三种肽配体和两种激活肽酶组成。内皮素系统成分多样的表达模式反映了其药理学复杂性，这些成分具有多种生理和病理生理作用。在血管中，内皮素系统具有基础血管收缩作用，并参与高血压、动脉粥样硬化和蛛网膜下腔出血后血管痉挛等疾病的发生发展。在心脏中，内皮素系统影响心肌收缩力和心率，并介导充血性心力衰竭中的心肌肥大和重塑。在肺中，内皮素系统调节气道和血管张力，并参与肺动脉高压的发生发展。在肾脏中，它控制水和钠的排泄以及酸碱平衡，并参与急性和慢性肾衰竭。在大脑中，内皮素系统调节心肺中枢和激素释放。对内皮素系统进行更深入的功能分析不仅需要使用高度特异性内皮素拮抗剂进行更多的药理学研究，还需要构建具有条件性功能丧失和功能获得操作的基因改造啮齿动物模型。
