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.
Wright
J W
JW
Department of Psychology, Washington State University, Pullman 99164-4820.
Hamilton
T A
TA
Harding
J W
JW
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D018826:CD13 Antigens / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D007276:Injections, Intraventricular; D019808:Losartan; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D013777:Tetrazoles; C066253:PD 123177; D018826:CD13 Antigens; D019808:Losartan