IN VIVO GENERATION AND ELIMINATION OF ANGIOTENSIN IN THE RAT

1. Combined high performance liquid chromatography (HPLC) and radio-immunoassays were used to study the in vivo kinetics of the renin-angiotensin system in the rat. The HPLC-verified plasma concentrations of angiotensin I (AI) were 1.0 nmol/L (0.52-1.6) in anaesthetized normal and 4.2 nmol/L (2.5-7.0) in salt-depleted rats. The plasma concentrations of angiotensin II (AII) were 0.07 nmol/L (0.04-0.13) in anaesthetized normal and 1.0 (0.60-1.6) nmol/L in salt-depleted rats. 2. The fate of injected AI and AII passing through the vascular bed of the lungs was determined. Two-thirds of the injected AI was converted to AII and one-third was unchanged after a single passage through the lungs. Only trace amounts of angiotensin III (AIII), the only other metabolite, were demonstrated. 3. This verifies that the majority of AI is metabolized through AII. Injected AII disappeared from the circulation with formation of only trace amounts of AIII, the half-life being about 10 s. This corresponds to a calculated in vivo generation rate of AII of about 12 nmol/L per h in normal rats. It is in agreement with the AI generation rate (plasma renin activity) measured as 9.5 nmol/L per h in vitro.