ANOMALOUS EFFECTS OF LOSARTAN ON AMINOPEPTIDASE-INDUCED REDUCTIONS OFBLOOD-PRESSURE IN SHR

The present investigation initially determined that a commercially ava ilable aminopeptidase M (AmM, Sigma Chemical) can lower blood pressure when intracerebroventricularly (ICV) infused in spontaneously hyperte nsive rats (SHR). Pretreatment with the angiotensin II (AngII) recepto r subtype 1 (AT(1)) antagonist, DuP 753 (losartan) significantly atten uated this hypotensive effect, in a dose-dependent manner, while pretr eatment with the AngII receptor subtype 2 (AT(2)) antagonist, PD123177 , did not influence AmM-induced hypotension. These results suggest tha t AT(1) receptors may be involved in the hypotension accompanying the ICV infusion of AmM; however, the relationship among available AT(1) s ites, angiotensin ligands, and peptidase activity appears to be compli cated with the likely involvement of additional, as yet unspecified, b rain peptide systems possessing cardiovascular action.