Faculty Collaboration Database

Organ specificity of angiotensin II and Des-aspartyl angiotensin II in the conscious rat. J Pharmacol Exp Ther 1976 Aug;198(2):450-6

Date

08/01/1976

Pubmed ID

948036

Scopus ID

2-s2.0-0017080309 (requires institutional sign-in at Scopus site)   23 Citations

Abstract

Des-Asp angiotensin II (des-Asp AII) is a naturally occurring heptapeptide metabolite of angiotensin II (AII) which is formed by the enzymatic action of aminopeptidase A. Angiotensin II and des-Asp AII were infused into unanesthetized rats while direct mean arterial pressure, serum aldosterone and serum corticosterone were measured. Both AII and des-Asp AII caused a dose-related increase in serum aldosterone with a significant increase occurring with a dose as low as 1 ng/min. This effect was blocked by pretreatment with 1-Sar-8-Ala-angiotensin II, a competitive inhibitor of AII; however, the inhibitor was more effective in blocking the effects of AII (101%) than of des-Asp AII (82%). Both angiotensins induced a dose-related increase in serum corticosterone and mean arterial pressure. Des-Asp AII was however only 1/10 as potent as AII in elevating mean arterial pressure. 1-Sar-8-Ala-AII was also effective in inhibiting the pressor effects of AII and des-Asp AII. These data illustrate a high degree of organ specificity or selectivity for des-Asp AII and a low specificity for AII. Aminopeptidase A and leucine aminopeptidase were identified in the adrenal cortex and medulla in large amounts. Des-Asp AII may thus be formed from AII locally in the adrenal gland prior to exerting its action at that site.

Author List

Campbell WB, Pettinger WA

Author

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenal Cortex
Adrenal Glands
Aldosterone
Aminopeptidases
Angiotensin II
Animals
Male
Rats
Receptors, Drug
Stimulation, Chemical