Mechanism of captopril-induced drinking

Area of Science:

• Pharmacology
• Neuroscience
• Endocrinology

Background:

• Angiotensin-converting enzyme (ACE) inhibitors are used to treat hypertension.
• The renin-angiotensin system plays a crucial role in regulating blood pressure and fluid balance.
• Captopril is an orally active ACE inhibitor.

Purpose of the Study:

• To investigate the mechanism by which oral captopril induces drinking and water diuresis in rats.
• To determine the role of the central and peripheral renin-angiotensin system in captopril's effects.
• To explore the distinct brain receptors for angiotensin II.

Main Methods:

• Rats were treated orally with captopril (100 mg.kg-1.day-1).
• Chronic intraperitoneal infusions of angiotensin II or [Sar1, Ile8]ANG II were administered.
• Intracerebroventricular (icv) infusions of captopril and [Sar1, Ile8]ANG II were performed.
• Drinking behavior and water diuresis were monitored.

Main Results:

• Oral captopril increased drinking and water diuresis in rats.
• Chronic systemic administration of angiotensin II or [Sar1, Ile8]ANG II abolished captopril's effects.
• Intracerebroventricular captopril reduced the dipsogenic response to oral captopril.
• Intracerebroventricular [Sar1, Ile8]ANG II did not affect captopril-induced drinking, suggesting distinct brain receptors for angiotensin II.

Conclusions:

• Oral captopril-induced drinking in rats is likely due to elevated angiotensin I levels from ACE blockade and stimulated renin secretion.
• Systemic angiotensin II may attenuate this response by reducing renin secretion.
• The study suggests distinct brain receptors for systemic and intracerebroventricular angiotensin II, with orally administered captopril not readily crossing the blood-brain barrier.