Angiotensin converting enzyme inhibitor captopril suppresses a genetic polydipsic behavior

Area of Science:

• Neuroscience
• Behavioral Science
• Pharmacology

Background:

• The STR/N mouse exhibits extreme polydipsia, consuming up to four times its body weight in fluids daily without physiological need.
• Angiotensin II (AII) is a known potent stimulator of drinking behavior, making it a potential factor in the STR/N mouse's condition.

Purpose of the Study:

• To investigate the role of angiotensin II in the polydipsia of STR/N mice.
• To determine the effect of captopril, an angiotensin converting enzyme inhibitor, on fluid consumption in STR/N mice and control subjects.

Main Methods:

• Oral administration of captopril to STR/N polydipsic mice and Swiss/Webster (S/W) normodipsic control mice.
• Quantification of daily water consumption in both groups before and after captopril treatment.

Main Results:

• Captopril administration reduced water consumption in STR/N mice by 46-79%.
• Conversely, captopril increased water consumption in S/W control mice by 20-42% in most subjects.
• These differential effects highlight a specific role for AII or related pathways in the mutant phenotype.

Conclusions:

• The polydipsic behavior in STR/N mice appears to be mediated, at least in part, by angiotensin II.
• Captopril's inhibitory action suggests that targeting the renin-angiotensin system could be a therapeutic strategy for similar conditions.
• The drug's effect on control mice suggests complex interactions within the fluid regulatory system.