Russell Fraser D
Vascular Biology Laboratory, Department of Medicine, The University of Queensland, Brisbane, The Prince Charles Hospital, Pathology Building, Rode Road, Ground Floor, Room 3, Chermside 4032, Queensland, Australia.
Pharmacol Ther. 2004 Sep;103(3):223-43. doi: 10.1016/j.pharmthera.2004.07.004.
Urotensin-II (UII) is a highly potent endogenous peptide within the cardiovascular system. Through stimulation of Galphaq-coupled UT receptors, UII mediates contraction of vascular smooth muscle and endothelial-dependent vasorelaxation, and positive inotropy in human right atrium and ventricle. A pathogenic role of the UT receptor system is emerging in cardiovascular disease states, with evidence for up-regulation of the UT receptor system in patients with congestive heart failure (CHF), pulmonary hypertension, cirrhosis and portal hypertension, and chronic renal failure. In vitro and in vivo studies show that under pathophysiological conditions, UII might contribute to cardiomyocyte hypertrophy, extracellular matrix production, enhanced vasoconstriction, vascular smooth muscle cell hyperplasia, and endothelial cell hyper-permeability. Single nucleotide polymorphisms of the UII gene may also impart a genetic predisposition of patients to diabetes. Therefore, the UT receptor system is a potential therapeutic target in the treatment of cardiac, pulmonary, and renal diseases. UT receptor antagonists are currently being developed to prevent and/or reverse the effects of over-activated UT receptors by the endogenous ligand. This review describes UII peptide and converting enzymes, and UT receptors in the cardiovascular system, focusing on pathophysiological roles of UII in the heart and blood vessels.
尾加压素II（UII）是心血管系统中一种高效的内源性肽。通过刺激与Gαq偶联的UT受体，UII介导血管平滑肌收缩、内皮依赖性血管舒张，以及人右心房和心室的正性肌力作用。UT受体系统在心血管疾病状态中正在显现出致病作用，有证据表明充血性心力衰竭（CHF）、肺动脉高压、肝硬化和门静脉高压以及慢性肾衰竭患者的UT受体系统上调。体外和体内研究表明，在病理生理条件下，UII可能导致心肌细胞肥大、细胞外基质产生、血管收缩增强、血管平滑肌细胞增生以及内皮细胞高通透性。UII基因的单核苷酸多态性也可能使患者具有患糖尿病的遗传易感性。因此，UT受体系统是治疗心脏、肺部和肾脏疾病的潜在治疗靶点。目前正在研发UT受体拮抗剂，以预防和/或逆转内源性配体过度激活UT受体的作用。这篇综述描述了心血管系统中的UII肽和转换酶以及UT受体，重点关注UII在心脏和血管中的病理生理作用。
