Angiotensin converting enzyme inhibitor captopril suppresses a genetic polydipsic behavior

The STR/N inbred mouse is a behavioral mutant that drinks up to four times its body weight in water or normal saline per day when given free access, despite the lack of physiological need. Since angiotensin II (AII) is a powerful elicitor of drinking behavior, we investigated the influence of the angiotensin converting enzyme inhibitor, captopril, on the amount of water consumed by the STR/N mouse. Oral administration of captopril, which inhibits formation of AII (active octapeptide) from AI (precursor decapeptide), resulted in a reduction of 46 to 79% in water consumption of 53 polydipsic STR/N mice, and a 20-42% increase in water consumption of 12 of 13 Swiss/Webster (S/W) normodipsic control mice. These results suggest that the polydipsic behavior of the STR/N mutant may involve mediation by AII and/or another molecule which is also suppressed by captopril, such as another peptide, which, for activation, requires cleavage by a peptidase which is inhibited by captopril.