Anomalous effects of losartan on aminopeptidase-induced reductions of blood pressure in SHR.

The present investigation initially determined that a commercially available aminopeptidase M (AmM, Sigma Chemical) can lower blood pressure when intracerebroventricularly (ICV) infused in spontaneously hypertensive rats (SHR). Pretreatment with the angiotensin II (AngII) receptor subtype 1 (AT1) antagonist, DuP 753 (losartan) significantly attenuated this hypotensive effect, in a dose-dependent manner, while pretreatment with the AngII receptor subtype 2 (AT2) antagonist, PD123177, did not influence AmM-induced hypotension. These results suggest that AT1 receptors may be involved in the hypotension accompanying the ICV infusion of AmM; however, the relationship among available AT1 sites, angiotensin ligands, and peptidase activity appears to be complicated with the likely involvement of additional, as yet unspecified, brain peptide systems possessing cardiovascular action.