Comparison of the effects of the dipeptidyl peptidase inhibitors captopril, ramipril, and enalapril on water intake and sodium appetite of Sprague-Dawley rats.
Two experiments were performed with Sprague-Dawley rats to study the effects of different inhibitors of angiotensin I converting enzyme (ACE) on water intake and sodium appetite. Subcutaneous administration of low doses of either enalapril (MK421) or ramipril (Hoe498), like captopril, was dipsogenic. Acute administration of ramipril also enhanced the drinking response to peripherally administered angiotensin I (Ang I). Higher doses inhibited the drinking response to Ang I, administered acutely either peripherally or centrally. These data provide behavioral evidence that the nonsulfhydryl inhibitors enalapril and ramipril inhibit brain converting enzyme activity and that they are considerably more potent than captopril. All three of these compounds, administered chronically in food, induced an appetite for sodium chloride (NaCl) solution. Enalapril and ramipril were more potent than captopril. Plasma renin activity was increased by each of these inhibitors, but the magnitude of the increase was not clearly related to the amount of NaCl consumed. The water intake in response to acute administration of either Ang I or isoproterenol was not reliably increased in rats treated chronically with these inhibitors.
Rowland
N E
NE
Center for Neurobiological Sciences, University of Florida, Gainesville 32611.
Fregly
M J
MJ
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001066:Appetite / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects*; D004656:Enalapril / Q000494:pharmacology*; D017257:Ramipril; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood; D012965:Sodium Chloride / Q000008:administration & dosage*
D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D000804:Angiotensin II; D012965:Sodium Chloride; D004656:Enalapril; D000803:Angiotensin I; D002216:Captopril; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D012083:Renin; D017257:Ramipril