Pressor responses to amastatin, bestatin and Plummer's inhibitors are suppressed by pretreatment with the angiotensin receptor antagonist sarthran.
The aminopeptidase inhibitors, amastatin (AM) and bestatin (BE), and carboxypeptidase inhibitor Plummer's (PL) were applied intracerebroventricularly (ICV) in rats following pretreatment with the angiotensin receptor antagonist sarthran (Sar1,Thr8-AII) or artificial cerebrospinal fluid. Angiotensin II (AII) was also included as a comparison vasoactive peptide. Pressor responses were recorded at 30 min intervals for 90 min to ascertain the duration of the antagonistic effect of sarthran on subsequent injections of AM, BE, PL and AII. Sarthran was effective in suppressing pressor activity to AII- and PL-induced pressor activity until 60 min following pretreatment, and AM- and BE-induced pressor responses until 90 min following pretreatment. These data suggest that AM, BE and PL are having their pressor effects via the central angiotensinergic system and that the patterns of AM, BE, PL and AII recovery from the influence of a specific angiotensin receptor antagonist are similar. The results are consistent with the concept that these inhibitors may increase endogenously synthesized angiotensins which are associated with pressor responses.
Batt
C M
CM
Department of Psychology, Washington State University, Pullman 99164-4830.
Klein
E W
EW
Harding
J W
JW
Wright
J W
JW
D000626:Aminopeptidases / Q000378:metabolism; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007276:Injections, Intraventricular; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology*
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D010455:Peptides; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C014805:angiotensin II, Sar(1)-Thr(8)-; C016977:amastatin; D002268:Carboxypeptidases; D000626:Aminopeptidases; D007930:Leucine; C012211:ubenimex