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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Endothelin: 20 years from discovery to therapy.
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Endothelin: 20 years from discovery to therapy.

机译：内皮素：从发现到治疗的20年。

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摘要

Since its identification as an endothelial cell-derived vasoconstrictor peptide in 1988, endothelin-1, the predominant member of the endothelin peptide family, has received considerable interest in basic medical science and in clinical medicine, which is reflected by more than 20 000 scientific publications on endothelin research in the past 20 years. The story of endothelin is unique as the gene sequences of endothelin receptors and the first receptor antagonists became available within only 4 years of the identification of the peptide sequence.The first clinical study in patients with congestive heart failure was published only 3 years thereafter. Yet, despite convincing experimental evidence of a pathogenetic role for endothelin in development, cell function, and disease, many initial clinical studies on endothelin antagonism were negative. In many of these studies, study designs or patient selection were inadequate. Today, for diseases such as pulmonary hypertension, endothelin antagonist treatmenthas become reality in clinical medicine, and ongoing clinical studies are evaluating additional indications, such as renal disease and cancer. Twenty years after the discovery of endothelin, its inhibitors have finally arrived in the clinical arena and are now providing us with new options to treat disease and prolong the lives of patients. Possible future indications include resistant arterial hypertension, proteinuric renal disease, cancer, and connective tissue diseases.
机译：自1988年被鉴定为内皮细胞衍生的血管收缩肽以来，内皮素肽家族的主要成员内皮素-1在基础医学和临床医学中引起了极大的兴趣，这已被2万多本科学出版物所反映。在过去20年中对内皮素的研究内皮素的故事是独一无二的，因为在鉴定肽序列后仅4年内即可获得内皮素受体的基因序列，并且在3年后才发表了第一个针对充血性心力衰竭患者的临床研究。然而，尽管有令人信服的实验证据表明内皮素在发育，细胞功能和疾病中具有致病作用，但许多有关内皮素拮抗作用的初步临床研究仍为阴性。在许多此类研究中，研究设计或患者选择都不充分。如今，对于诸如肺动脉高压的疾病，内皮素拮抗剂治疗已成为临床医学中的现实，并且正在进行的临床研究正在评估其他适应症，例如肾脏疾病和癌症。内皮素的发现已经二十年了，它的抑制剂终于进入临床领域，现在为我们提供了治疗疾病和延长患者寿命的新选择。未来可能的适应症包括耐药性高血压，蛋白尿肾病，癌症和结缔组织病。

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