des-Asp-angiotensin I: its identification in rat blood and confirmation as a substrate for converting enzyme

The observation that angiotensin III is present in the circulation of the rat in amounts similar to those of angiotensin II has led to the notion that it may, in part, be formed by the action of converting enzyme on des-Asp-angiotensin I without the prior formation of angiotensin II. This possibility was studied in conscious rats using a combination of RIA and chromatographic techniques which allowed the separate measurement of angiotensin I, des-Asp-angiotensin I, angiotensin II, and angiotensin III in rat blood. Infusion of des-Asp1-[Ile5]angiotensin I at 50, 150, and 450 ng/kg . min resulted in a progressive increase in the plasma concentration of angiotensin III up to 279 +/- 50 (SD) pg/ml compared to 9 +/- 9 (SD) pg/ml after dextrose infusion. Regardless of the infusion of des Asp-[Ile5]angiotensin I, plasma angiotensin III made up a constant 46 +/- 8% (+/- SD) of the total immunoactive material, the remainder being composed of smaller metabolic fragments, indicating a rapid rate of clearance of angiotensin III. Captopril completely inhibited the rise in angiotensin III after des-Asp1-[Ile5]angiotensin I infusion. A substance which chromatographed as des-Asp-[Ile5]angiotensin I was detected in rat blood and made up 19% of the angiotensin I immunoactive material, while angiotensin III made up 44% of the angiotensin II immunoactive material. These results confirm that des-Asp1-[Ile5]angiotensin I is a substrate for converting enzyme in the rat, and the presence of a chromatographically similar substance in the circulation suggests that at least part of the angiotensin III in rat blood may be formed by the action of converting enzyme on endogenous des-Asp-angiotensin I. (Endocrinology 108: 406, 1981)