Release of adrenal catecholamines by angiotensin I.

Abstract

A structure activity study was attempted to determine the optimum angiotensin (Ang) peptide chain length for adrenal medullary stimulation. Isolated cat adrenal glands were retrograde perfused at a flow rate of 1 ml/min with phosphate-buffered Locke9s solution at 23-25°C. Continuous catecholamine analysis was performed with an automated trihydroxyindole procedure. All drugs were administered either by close single injection (0.05-0.1 ml) or by perfusion. Ang series peptides administered were His-Pro-Phe; Val-Tyr-Ileu-His-Pro-Phe; Arg-Val-Tyr-Ileu-His-Pro-Phe; 1-Aap(NH 2 )-5-Val-Ang II; 1-Asp-5-Ileu Aug I and II; 1-Asp-5-Ileu-tetradecapeptide (renin substrate); 1-Asp-5-Ileu-8-Ala-Ang II. The optimum Ang chain length for adrenal medullary stimulation appeared to be 8 to 10 amino acids. There was cross-tachyphylaxis between the active peptides. Sustained catecholamine secretion was induced by administering the peptides via perfusion. Peptide-induced adrenal catecholamine secretion required Ca ++ . Since Aug I is an extremely potent peptide, studies were performed with 1O- 14 C-Leu-Ang I or antibody for 1-Asp-5-Ileu-Ang II to determine if the decapeptide was acting indirectly through conversion to Ang II. Ang I was found to have a marked, direct effect on the isolated adrenal medulla.