Angiotensin-converting enzyme 2: a new target for neurogenic hypertension

被引:37
作者
Feng, Yumei
Xia, Huijing
Santos, Robson A. [3 ]
Speth, Robert [4 ]
Lazartigues, Eric [1 ,2 ]
机构
[1] Louisiana State Univ, Hlth Sci Ctr, Sch Med, Dept Pharmacol & Expt Therapeut, New Orleans, LA 70112 USA
[2] Louisiana State Univ, Hlth Sci Ctr, Cardiovasc Ctr Excellence, New Orleans, LA 70112 USA
[3] Univ Fed Minas Gerais, Dept Physiol & Biophys, Belo Horizonte, MG, Brazil
[4] Nova SE Univ, Coll Pharm, Dept Pharmaceut Sci, Ft Lauderdale, FL 33328 USA
关键词
BLOOD-PRESSURE; NITRIC-OXIDE; RENIN; SYSTEM; OVEREXPRESSION; RESPONSES; BRAIN; RATS; MICE; ANGIOTENSIN-CONVERTING-ENZYME-2;
D O I
10.1113/expphysiol.2009.047407
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Overactivity of the renin-angiotensin system (RAS) is involved in the pathogenesis of hypertension, and an overactive brain RAS has been highlighted in several genetic and experimental models. Until now, angiotensin II (Ang II) was thought to be the main effector of this system, and the angiotensin-converting enzyme (ACE)-Ang II-Ang II type 1 receptor axis was the main target for antihypertensive therapies. A new member of the RAS, ACE2 (angiotensin-converting enzyme type 2), has been identified in organs and tissues related to cardiovascular function (e.g. heart, kidney and blood vessels) and appears to be part of a counter-regulatory pathway to buffer the excess of Ang II. We recently identified the ACE2 protein in brain regions involved in the central regulation of blood pressure and showed that it regulates, and is regulated by, other components of the RAS. Here, we present evidence for the involvement of brain ACE2 in the central regulation of blood pressure, autonomic and cardiac function. We show that lack of ACE2 is deleterious for the central regulation of blood pressure and that brain ACE2 gene therapy can restore baroreflex and autonomic functions and prevent the development of hypertension. Additionally, and independently of a reduction in Ang II levels, we will highlight some of the mechanisms responsible for the beneficial effects of central ACE2 in cardiovascular function.
引用
收藏
页码:601 / 606
页数:6
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