The reduction in alcohol intake produced by enalapril is not attenuated by centrally administered angiotensin inhibitors.
Angiotensin-converting enzyme (ACE) inhibitors, which prevent the conversion of angiotensin I to angiotensin II, reduce alcohol intake when injected peripherally. The mechanism by which ACE inhibitors produce this effect on alcohol intake is unknown. A rise in the biosynthesis of angiotensin II in the periphery is known to reduce alcohol intake. In this experiment, we examine the possibility that the reduction in alcohol intake produced by an ACE inhibitor, enalapril, is mediated by a rise in angiotensin II in the brain. Enalapril, 20 mg/kg, injected intraperitoneally, produced a 40% reduction in alcohol intake. This reduction was not attenuated by the concurrent administration into the lateral ventricle of either the ACE inhibitors captopril or ceranapril (1, 10, or 25 micrograms), or the angiotensin II receptor antagonist Sar1-Thr8-Angiotensin II (5 micrograms). These findings suggest that the ACE inhibitors do not reduce alcohol intake by raising angiotensin II in the brain.
Robertson
J M
JM
Department of Pharmacology, University of Toronto, Ontario, Canada.
Harding
S
S
Grupp
L A
LA
D000428:Alcohol Drinking; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology*; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D009943:Organophosphorus Compounds; D000804:Angiotensin II; C014805:angiotensin II, Sar(1)-Thr(8)-; D004656:Enalapril; D011392:Proline; D002216:Captopril; C054518:ceronapril