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[肾素-血管紧张素-醛固酮系统:简史及与2019冠状病毒病大流行相关的问题]

[Renin-angiotensin-aldosterone system : brief history and questions related to the COVID-19 pandemic].

作者信息

Valdes-Socin H, Jouret F, Vroonen L, Scheen A J, Lancellotti P

机构信息

Service d'Endocrinologie, CHU Liège, Belgique.

Service de Néphrologie, CHU Liège, Belgique.

出版信息

Rev Med Liege. 2020;75(S1):123-129.

Abstract

The breakthrough of the secrets of hypertension and the renin-angiotensin-aldosterone system (RAAS) is one of the legends of medicine. The first chapter is the one of Tigerstedt's experiments about renin, and Loesch and Gollblatt's model of renal hypertension. The race to elucidate the mechanisms of angiotensin, angiotensinogen and the angiotensin conversion enzyme cascade, by Braun Menéndez and Page teams, is a second chapter. The puzzle of this elegant cascade is completed by aldosterone isolation by the collaboration of Tait spouses and Tadeus Rechstein. As a corollary of these findings, Conn made the first description of primary hyperaldosteronism. The elucidation of RAAS pathophysiology naturally led to the synthesis of the antihypertensive captopril by Ondetti and Cushman, thereby opening the modern era of ACE inhibitors and ARII blockers. In March 2020, a viral pandemic caused by SARS-Cov-2 ignites the entire planet. This new coronavirus uses the RAAS angiotensin conversion enzyme type 2 (ACE-2) as a gateway. The SARS-CoV-2/ACE-2 signalling pathway and its pathological effects on the cardio-respiratory and renal system of these patients initiate a new chapter. The interaction of SARS-Cov-2/ACE-2 axis with anti-hypertensive agents, as well as with ACE-2 activators and ACE-2 homologs, takes a part of an active international study searching for therapeutic targets. This modern research, summarized in this article, will further develop our knowledge of RAAS and, hopefully, will improve the management of COVID-19 patients.

摘要

高血压及肾素 - 血管紧张素 - 醛固酮系统(RAAS)奥秘的突破是医学传奇之一。第一章是蒂格斯特德关于肾素的实验,以及勒施和戈德布拉特的肾性高血压模型。布劳恩·梅嫩德斯和佩奇团队对血管紧张素、血管紧张素原及血管紧张素转换酶级联反应机制的探索是第二章。泰特夫妇与塔德乌斯·雷施泰因合作分离出醛固酮,完善了这一精妙级联反应的谜题。作为这些发现的必然结果,康恩首次描述了原发性醛固酮增多症。RAAS病理生理学的阐明自然地促使翁代蒂和库什曼合成了抗高血压药物卡托普利,从而开启了ACE抑制剂和ARII阻滞剂的现代时代。2020年3月,由SARS-CoV-2引发的病毒性大流行席卷全球。这种新型冠状病毒将RAAS中的血管紧张素转换酶2型(ACE-2)作为进入途径。SARS-CoV-2/ACE-2信号通路及其对这些患者心肺和肾脏系统的病理影响开启了新的篇章。SARS-CoV-2/ACE-2轴与抗高血压药物以及ACE-2激活剂和ACE-2同源物的相互作用,成为了一项积极的国际研究寻找治疗靶点的一部分。本文总结的这项现代研究将进一步拓展我们对RAAS的认识,并有望改善COVID-19患者的治疗管理。

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