Distribution of Fos-immunoreactivity in rat brain following a dipsogenic dose of captopril and effects of angiotensin receptor blockade.
Immunohistochemical techniques were used to detect Fos in the brain following subcutaneous administration of the angiotensin converting enzyme inhibitors captopril or enalapril at 0.5 mg/kg to conscious rats. Increased Fos-like immunoreactivity was observed in many neurons in the lamina terminalis, and in regions of the hypothalamus. Captopril at this dose also caused water drinking in other rats. Pre-treatment with the angiotensin AT1 receptor antagonist ZD7155 (10 mg/kg) given subcutaneously prevented the captopril-induced increase in Fos in the lamina terminalis. This dose of ZD7155 also prevented captopril-induced drinking in other rats. With a higher dose (50 mg/kg) of captopril or enalapril, there was no increase in Fos in the lamina terminalis. This dose of captopril was not dipsogenic. The results are consistent with the proposal that the lower dose (0.5 mg/kg) of captopril or enalapril increases circulating angiotensin I levels which are then converted to angiotensin II in the organum vasculosum of the lamina terminalis and subfornical organ. Stimulation of neurons at these sites may subserve water drinking and sodium appetite.
McKinley
M J
MJ
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
Colvill
L M
LM
Giles
M E
ME
Oldfield
B J
BJ
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology*; D004326:Drinking / Q000187:drug effects*; D004656:Enalapril / Q000494:pharmacology; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009287:Naphthyridines / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D009287:Naphthyridines; D016760:Proto-Oncogene Proteins c-fos; C095905:ZD 7155; D000804:Angiotensin II; D004656:Enalapril; D000803:Angiotensin I; D002216:Captopril