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

Yumei Feng1, Huijing Xia, Robson A Santos

  • 1Louisiana State University Health Sciences Center, School of Medicine, Department of Pharmacology and Experimental Therapeutics, 1901 Perdido Street, New Orleans, LA 70112, USA.

Experimental Physiology
|November 20, 2009
PubMed

Insights

Brain ACE2 (angiotensin-converting enzyme type 2) is crucial for regulating blood pressure and autonomic function. Gene therapy restoring brain ACE2 can prevent hypertension and restore cardiovascular function.

Area of Science:

  • Cardiovascular Science
  • Neuroscience
  • Genetics

Background:

  • The renin-angiotensin system (RAS) plays a key role in hypertension.
  • The angiotensin-converting enzyme (ACE)-angiotensin II (Ang II)-Ang II type 1 receptor axis has been the primary therapeutic target.
  • ACE2 (angiotensin-converting enzyme type 2) is a newly identified RAS component acting as a counter-regulatory pathway to Ang II.

Purpose of the Study:

  • To investigate the role of brain ACE2 in the central regulation of blood pressure, autonomic, and cardiac function.
  • To explore the therapeutic potential of brain ACE2 in preventing and treating hypertension.

Main Methods:

  • Identification of ACE2 protein in brain regions regulating blood pressure.
  • Assessment of the effects of ACE2 deficiency on blood pressure regulation and autonomic function.
  • Evaluation of brain ACE2 gene therapy for restoring baroreflex and autonomic functions and preventing hypertension.

Main Results:

  • Lack of ACE2 in the brain impairs central blood pressure regulation.
  • Brain ACE2 gene therapy restores baroreflex and autonomic functions.
  • Gene therapy prevents the development of hypertension.
  • Beneficial effects of central ACE2 on cardiovascular function are partly independent of Ang II reduction.

Conclusions:

  • Brain ACE2 is essential for the central regulation of blood pressure and autonomic control.
  • Targeting brain ACE2 offers a promising therapeutic strategy for hypertension and related cardiovascular dysfunction.

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