Increased blood pressure induced by central application of aminopeptidase inhibitors is angiotensinergic-dependent in normotensive and hypertensive rat strains.
Two aminopeptidase inhibitors, amastatin (AM) and bestatin (BE), were employed in 3 strains of rats, spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD), to investigate the central angiotensinergic system. The results indicate that intracerebroventricular (i.c.v.) injections of AM and BE induced pressor elevations in all 3 strains of rats. In order to test for the possibility of spillage into peripheral vasculature, members from all 3 strains were peripherally infused with AM, BE, or 0.15 NaCl via jugular vein catheters. The SHRs were significantly more responsive to the aminopeptidases than the normotensive strains, however their overall pressor responses were only 33% of those to i.c.v. infusion. Next, in order to test the notion that these aminopeptidase inhibitors are having their effect via the central angiotensinergic system, and not some other peptidergic system, the specific angiotensin receptor antagonist, Sar1, Thr8-AII (sarthran) was employed. Intracerebroventricular pretreatment with sarthran prevented subsequent pressor responses to i.c.v. AM and BE in members of all 3 strains, thereby suggesting that these aminopeptidase inhibitors are having their effect via the central angiotensinergic system.
Department of Psychology, Washington State University, Pullman 99164-4830.
L L
LL
Jensen
J W
JW
Harding
J W
JW
Wright
D000626:Aminopeptidases / Q000378:metabolism*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D000900:Anti-Bacterial Agents; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000201:enzymology* / Q000378:metabolism; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides; D051381:Rats; D011918:Rats, Inbred SHR; 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; D000626:Aminopeptidases; D007930:Leucine; C012211:ubenimex