Organ specificity of angiotensin II and Des-aspartyl angiotensin II in the conscious rat.
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.
D000302:Adrenal Cortex / Q000187:drug effects; D000311:Adrenal Glands / Q000201:enzymology; D000450:Aldosterone / Q000378:metabolism; D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D008297:Male; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects; D013268:Stimulation, Chemical
D011955:Receptors, Drug; D000804:Angiotensin II; D000450:Aldosterone; D000626:Aminopeptidases