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血管紧张素-(1-7):心血管控制中的转化途径。

Angiotensin-(1-7): Translational Avenues in Cardiovascular Control.

机构信息

Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, Pennsylvania, USA.

出版信息

Am J Hypertens. 2019 Nov 15;32(12):1133-1142. doi: 10.1093/ajh/hpz146.

Abstract

Despite decades of research and numerous treatment approaches, hypertension and cardiovascular disease remain leading global public health problems. A major contributor to regulation of blood pressure, and the development of hypertension, is the renin-angiotensin system. Of particular concern, uncontrolled activation of angiotensin II contributes to hypertension and associated cardiovascular risk, with antihypertensive therapies currently available to block the formation and deleterious actions of this hormone. More recently, angiotensin-(1-7) has emerged as a biologically active intermediate of the vasodilatory arm of the renin-angiotensin system. This hormone antagonizes angiotensin II actions as well as offers antihypertensive, antihypertrophic, antiatherogenic, antiarrhythmogenic, antifibrotic and antithrombotic properties. Angiotensin-(1-7) elicits beneficial cardiovascular actions through mas G protein-coupled receptors, which are found in numerous tissues pivotal to control of blood pressure including the brain, heart, kidneys, and vasculature. Despite accumulating evidence for favorable effects of angiotensin-(1-7) in animal models, there is a paucity of clinical studies and pharmacokinetic limitations, thus limiting the development of therapeutic agents to better understand cardiovascular actions of this vasodilatory peptide hormone in humans. This review highlights current knowledge on the role of angiotensin-(1-7) in cardiovascular control, with an emphasis on significant animal, human, and therapeutic research efforts.

摘要

尽管经过了几十年的研究和多种治疗方法,高血压和心血管疾病仍然是全球主要的公共卫生问题。肾素-血管紧张素系统是调节血压和高血压发展的主要因素之一。特别值得关注的是,血管紧张素 II 的不受控制的激活导致了高血压和相关的心血管风险,目前可用的抗高血压疗法可阻止这种激素的形成和有害作用。最近,血管紧张素-(1-7)作为肾素-血管紧张素系统血管舒张臂的一种具有生物活性的中间产物而出现。这种激素拮抗血管紧张素 II 的作用,并具有抗高血压、抗心肌肥厚、抗动脉粥样硬化、抗心律失常、抗纤维化和抗血栓形成作用。血管紧张素-(1-7)通过 mas G 蛋白偶联受体引起有益的心血管作用,这些受体存在于许多组织中,这些组织对于控制血压至关重要,包括大脑、心脏、肾脏和血管。尽管有越来越多的证据表明血管紧张素-(1-7)在动物模型中具有有利的作用,但临床研究和药代动力学限制的缺乏,限制了治疗剂的开发,以更好地了解这种血管舒张肽激素在人类中的心血管作用。这篇综述强调了血管紧张素-(1-7)在心血管控制中的作用,重点介绍了重要的动物、人类和治疗研究工作。

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