The brain angiotensin system: subcellular localization and interferences with converting enzyme inhibitors

Area of Science:

• Neuroscience
• Cardiovascular Research
• Biochemistry

Background:

• The renin-angiotensin system (RAS) plays a crucial role in blood pressure regulation.
• Components of the RAS have been identified in the brain, but their intracellular localization and function remain incompletely understood.

Purpose of the Study:

• To investigate the subcellular localization of renin and angiotensin II (ANG II) within the rat brain.
• To explore the potential for intracellular synthesis of ANG II in the brain.
• To assess the role of brain RAS in blood pressure regulation, particularly in spontaneously hypertensive rats.

Main Methods:

• Electron microscopy was used to demonstrate the presence and localization of renin and ANG II in rat brain synaptosomes.
• Biochemical analysis confirmed the identity of brain ANG II.
• Nephrectomy and angiotensin-converting enzyme (ACE) blockade were employed to study peptide levels and accumulation in vivo.
• Studies were conducted in stroke-prone spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY).

Main Results:

• Renin was found in synaptosomes, separate from cathepsin D and intraneuronal ANG II.
• Intracellular synthesis of ANG II in the brain is suggested by these findings.
• Brain ANG II is biochemically identical to plasma ANG II.
• Nephrectomy did not alter brain peptide levels, but ACE blockade led to ANG I accumulation.
• SHR exhibited higher ANG I accumulation and lower ANG II levels compared to WKY, indicating increased ANG II synthesis and turnover.
• Converting enzyme inhibitors (CEI) penetrate the brain and may lower blood pressure by inhibiting the brain RAS.

Conclusions:

• The brain possesses components of the RAS, including renin and ANG II, within synaptosomes, suggesting local synthesis.
• The brain RAS is biochemically similar to the peripheral RAS.
• The brain RAS plays a role in blood pressure regulation, and its inhibition by CEI may contribute to their antihypertensive effects.