Effect of chronic treatment with trandolapril or enalapril on brain ACE activity in spontaneously hypertensive rats.
The aim of the present study was to determine whether the new ACE inhibitor trandolapril was able to inhibit brain ACE activity in spontaneously hypertensive rats (SHRs). Therefore, we have measured ex vivo ACE activity in discrete brain areas of SHRs after a 2-week oral treatment with trandolapril (0.001, 0.01, 0.1 and 1 mg/kg/day). The effects of trandolapril were compared to those of enalapril (10 mg/kg/day), used as a reference compound. Enalapril induced a decrease in ACE activity in brain areas not protected by the blood brain barrier (subfornical organ and median eminence) and in cerebral cortex. Conversely, trandolapril at a dose of 0.01 mg/kg/day and above induced a dose-dependent inhibition of ACE activity in all brain areas assayed, including the supraoptic and paraventricular hypothalamic nuclei, septum, amygdala, hippocampus, cerebellar and cerebral cortex, nucleus of the tractus solitary and caudate nucleus. The inhibition was roughly similar in all brain areas studied. These data suggest that after chronic oral administration in SHRs, trandolapril or its metabolite, in contrast to enalapril or enalaprilat, was able to reach all brain areas of SHRs, including those protected by the blood brain barrier.
Jouquey
S
S
Centre de Recherche Roussel-Uclaf, Romainville, France.
Mathieu
M N
MN
Hamon
G
G
Chevillard
C
C
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C052035:trandolapril; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A