Converting enzyme activity and angiotensin metabolism in the dog brainstem.
The concentrations of angiotensin converting enzyme (ACE) activity, norepinephrine, and serotonin were measured in microdissected regions of the dog's brainstem and spinal cord. In addition, we determined the in vitro metabolism of 125I-angiotensin I (Ang I) in homogenates of the same brain punch regions. High ACE-specific activity was found in the monoamine-containing regions of the brainstem and in the intermediolateral column of the spinal cord. In brainstem homogenates 125I-Ang I was metabolized to angiotensin II (Ang-[1-8]) and the N-terminal heptapeptide Ang-(1-7). In the presence of MK 422 (50 microM), Ang-(1-7) was still generated, while the production of Ang-(1-8) was inhibited. This study revealed the presence of high ACE activity in monoamine regions of dog brainstem and spinal cord, and showed that the metabolite Ang-(1-7) is the major product generated from Ang I in the presence and absence of ACE inhibition.
Santos
R A
RA
Department of Brain and Vascular Research, Cleveland Clinic Foundation, OH 44195.
Brosnihan
K B
KB
Chappell
M C
MC
Pesquero
J
J
Chernicky
C L
CL
Greene
L J
LJ
Ferrario
C M
CM
D000803:Angiotensin I / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D004285:Dogs; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D015773:Enalaprilat; D009638:Norepinephrine / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D010446:Peptide Fragments; D012701:Serotonin; D004656:Enalapril; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat; D009638:Norepinephrine