Differential effects of aminopeptidase inhibitors on angiotensin-induced pressor responses.
Recent iontophoretic data suggest that conversion of angiotensin II (AII) to angiotensin III (AIII) may be necessary before the peptide can activate central angiotensin-sensitive neurons. Furthermore, this conversion may be inhibited by the aminopeptidase A inhibitor, amastatin. In the present study we investigated the importance of aminopeptidase activity on central angiotensin-induced pressor responses. Intracerebroventricular (i.c.v.) pretreatment with amastatin, suppressed i.c.v. AII-induced pressor responses. Pretreatment with the aminopeptidase B inhibitor, bestatin, increased pressor responses to AIII. Pressor responses induced by the aminopeptidase-resistant analogue, [Sar1]angiotensin II, were not affected by pretreatment with angiotensin inhibitors. These results support the hypothesis that AII must be converted to AIII to be active in the brain.
Sullivan
M J
MJ
Department of Psychology, Washington State University, Pullman 99164.
Harding
J W
JW
Wright
J W
JW
D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000804:Angiotensin II / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000805:Angiotensin III / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents; D001794:Blood Pressure / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D000900:Anti-Bacterial Agents; D009842:Oligopeptides; D010455:Peptides; D000804:Angiotensin II; D000805:Angiotensin III; C032651:angiotensin II, Sar(1)-Ile(5)-; C016977:amastatin; D000626:Aminopeptidases; D007930:Leucine; C012211:ubenimex