Brain angiotensin: pathways and pharmacology

Area of Science:

• Neuroscience
• Cardiovascular Physiology
• Pharmacology

Background:

• The brain renin-angiotensin system (RAS) is a recognized entity within various tissue RASs.
• Angiotensin pathways in brain regions regulating central blood pressure are identified.
• Evidence suggests the brain RAS functions independently of the hormonal RAS.

Purpose of the Study:

• To investigate the role of the brain RAS in blood pressure regulation and body fluid homeostasis.
• To explore the contribution of the brain RAS to hypertension, particularly in spontaneously hypertensive rats.
• To examine the effects of angiotensin-converting enzyme (ACE) inhibitors on the brain RAS and blood pressure.

Main Methods:

• Biochemical, neurophysiologic, pharmacologic, and molecular genetic studies.
• Analysis of angiotensin pathways in central blood pressure regulatory areas.
• Administration of ACE inhibitors centrally and systemically in spontaneously hypertensive rats.

Main Results:

• The brain RAS is regulated independently of the hormonal RAS.
• An overactive brain RAS may contribute to hypertension pathogenesis and maintenance.
• Central administration of ACE inhibitors lowered blood pressure in spontaneously hypertensive rats by acting on the brain.

Conclusions:

• The brain RAS is integral to blood pressure control and body fluid homeostasis.
• Brain RAS overactivity is implicated in the development and maintenance of hypertension.
• The efficacy of ACE inhibitors in hypertension may depend on their ability to penetrate the brain and inhibit brain ACE.