Central effects of converting enzyme inhibitors

Area of Science:

• Neuroscience
• Cardiovascular Physiology
• Pharmacology

Background:

• Systemic administration of converting enzyme inhibitors (CEI) inhibits the plasma renin-angiotensin system (RAS).
• CEI may also inhibit the RAS in target organs, including the brain, potentially influencing blood pressure (BP) regulation.

Purpose of the Study:

• To investigate the role of central nervous system (CNS) converting enzyme (CE) inhibition by CEI in blood pressure regulation.
• To determine if CEI can inhibit brain CE and affect BP in hypertensive rats.

Main Methods:

• Administered CEI intracerebroventricularly (i.c.v.) and peripherally in stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto (WKY) controls.
• Assessed pressor and drinking responses to i.c.v. angiotensin I (ANG I) and renin.
• Measured CE activity in brain tissue and brain RAS parameters after chronic oral CEI treatment.

Main Results:

• I.c.v. CEI inhibited pressor and drinking responses to i.c.v. ANG I and renin, and potentiated responses to bradykinin.
• I.c.v. captopril lowered BP in SHRSP but not WKY rats.
• Peripheral CEI administration inhibited brain CE, and chronic oral treatment altered brain RAS parameters, suggesting reduced ANG II formation.

Conclusions:

• Converting enzyme inhibition within the brain contributes to the blood pressure-lowering effects of CEI.
• CEI can inhibit central CE, impacting the brain's renin-angiotensin system.
• Brain CE inhibition by CEI is a significant factor in their antihypertensive action.