Human urotensin-II, the most potent mammalian vasoconstrictor identified to date, as a therapeutic target for the management of cardiovascular disease
Human urotensin-II, the most potent mammalian vasoconstrictor identified to date, as a therapeutic target for the management of cardiovascular disease
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DOI：
10.1016/s1050-1738(00)00069-4
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发表时间：
2000-08-01
影响因子：
9.3
通讯作者：
Ohlstein, EH
中科院分区：
文献类型：
--
作者：
Douglas, SA;Ohlstein, EH
新型环状十一肽人尾加压素-II（hU-II）及其高亲和力G蛋白偶联受体GPR 14均在人心血管系统（血管平滑肌、内皮、心肌、冠状动脉粥样硬化等）中表达。因此，可能有助于人类心血管稳态的（病理）生理调节。实际上，hU-II是哺乳动物分离血管的有效、持续的痉挛原，所述哺乳动物分离血管包括来自大鼠、兔、狗、猪、非人灵长类动物和人的那些（其中它比内皮素（ET）-1更有效一至两个数量级）。在体内，hU-II显著改变麻醉灵长类动物的全身血液动力学（上箭头心脏收缩力[dP/dt]，上箭头每搏输出量，下箭头总外周阻力），最终导致致命的心血管衰竭。因此，选择性hU-II受体拮抗剂的开发可用于控制以异常血管收缩、心肌功能障碍和/或心脏重塑为特征的心血管疾病（例如，心肌梗塞、充血性心力衰竭）。（Trends Endovasc Med 2000;10：229-237）。(C)2001年，Elsevier Science Inc.
The novel cyclic undecapeptide human urotensin-II (hU-II) and its high-affinity G-protein-coupled receptor, GPR14, are both expressed within the human cardiovasculature (vascular smooth muscle, endothelium, myocardium, coronary atheroma, etc.) and may, therefore, contribute to the (patho)physiological regulation of cardiovascular homeostasis in humans. Indeed, hU-II is an efficacious, sustained spasmogen of mammalian isolated blood vessels including those from rats, rabbits, dogs, pigs, non-human primates and humans (where it is one to two orders of magnitude more potent than endothelin (ET)-1). In vivo, hU-II markedly alters systemic hemodynamics in the anesthetized primate (up arrow cardiac contractility [dP/dt], up arrow stroke volume, down arrow total peripheral resistance) ultimately resulting in fatal cardiovascular collapse. As such, the development of selective hU-II receptor antagonists may be of utility in the management of cardiovascular disorders characterized by aberrant vasoconstriction, myocardial dysfunction and/or cardiac remodeling (e.g., myocardial infarction, congestive heart failure). (Trends Cardiovasc Med 2000;10:229-237). (C) 2001, Elsevier Science Inc.