Converting enzyme inhibitors and brain angiotensin

Area of Science:

• Pharmacology
• Cardiovascular Physiology
• Neuroendocrinology

Background:

• Spontaneously hypertensive rats (SHR) exhibit an overactive brain-angiotensin system.
• Converting enzyme inhibitors are potent hypotensive agents.
• Understanding the central mechanisms of blood pressure regulation is crucial.

Purpose of the Study:

• To investigate the mechanisms of blood pressure reduction by specific converting enzyme inhibitors in SHR.
• To compare the efficacy of intraventricular versus intravenous administration of these inhibitors.
• To assess the impact of these inhibitors on brain and plasma angiotensin II (ANG II) levels.

Main Methods:

• Administration of MK421, MK422, Hoe498, and ramiprilat via intraventricular (i.v.t.) and intravenous (i.v.) routes in SHR and Wistar-Kyoto rats (WKY).
• Measurement of blood pressure changes and duration of hypotensive effects.
• Quantification of brain and plasma angiotensin II (ANG II) levels using high-pressure liquid chromatography.

Main Results:

• Intraventricular MK421 was more potent than intravenous administration, causing prolonged blood pressure reduction in SHR.
• Ramiprilat prolonged blood pressure reduction in SHR but was less effective in WKY rats.
• Inhibitor administration differentially affected brain and plasma ANG II levels, with some increasing and others decreasing levels in specific brain regions.

Conclusions:

• Converting enzyme inhibitors exert hypotensive effects in SHR, potentially through mechanisms involving the brain-angiotensin system.
• The route of administration significantly influences the potency and duration of action of these inhibitors.
• Reduced brainstem ANG II in SHR treated with ramiprilat suggests baroreflex disinhibition as a potential mechanism for blood pressure lowering.