Oral administration of losartan influences aminopeptidase activity in the frontal cortex

Although there is a brain renin-angiotensin system, its mechanisms of contr ol are not fully understood. We studied the effect of oral administration o f the AT(1) receptor antagonist losartan on brain aminopeptidase (AP) activ ity, which plays a major role in neuropeptide metabolism. Six AP activities , related and non-related with the angiotensin (Ang) metabolism, were measu red in their soluble and membrane-bound forms in the frontal cortex of cont rol animals and rats treated with losartan, chronically administered via th e drinking water. The results demonstrate that soluble pGluAP and membrane- bound AspAP and GluAP increased significantly in losartan-treated animals, indicating that the blockade of the AT(1) receptor stimulates the activity of AP involved in the Ang metabolism. Moreover, the blockade of the AT(1) r eceptor induces changes not only in the brain angiotensin metabolism, but p robably also in that of other neuropeptides. (C) 2000 Elsevier Science B.V. All rights reserved.