Production and metabolic clearance of angiotensinogen in conscious rats as measured by steady-state isotope dilution

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Abstract
Previous studies on the hormonal regulation of hepatic angiotensinogen relied on in-vitro liver preparations and on the measurement of changes in plasma concentration. In this study 125I-labelled angiotensinogen was used to measure simultaneously the production rate (PR) and metabolic clearance rate (MCR) in conscious rats by the constant-rate infusion and single-injection methods. Male rats received daily s.c. injections of isotonic saline (as control), 1 mg corticosterone acetate (CA), 25 μg 17β-oestradiol benzoate (OB) or 20 μg thyroxine (T4) per 100 g body weight. On day 7 of treatment 125I-labelled angiotensinogen was infused into a jugular vein at a rate of 1 μl/h by osmotic minipumps and blood samples taken 4, 5 and 6 days later. The PR of angiotensinogen increased from 576 ± 28 (s.e.m.; n = 9) to 954 ± 63 (n = 9), 1010±84 (n = 9) and 2359±150 (n = 10) μg/h per kg following treatment with CA, OB and T4 respectively. In contrast, the PR of rat albumin did not change significantly from 218 ± 8 (n = 7) mg/h per kg. All three hormones increased MCR from 13 ± 1 (n = 17) ml/h per kg to 17± 1 (n = 9), 18 ± 2 (n = 9) and 27 ± 2 (n = 9) ml/h per kg for CA, OB and T4 respectively. Single-injection experiments on five rats showed angiotensinogen to be distributed into three compartments with a half-time of disappearance of 4·4 ± 1 min, 116±11 min and 13·1 ±2·6 h. It was concluded that the production of angiotensinogen in vivo is at least tenfold higher than the reported in-vitro rates, that the clearance of angiotensinogen is under hormonal regulation and that angiotensinogen is distributed between at least three compartments. J. Endocr. (1987) 112, 391–397