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Rat plasma contains two distinct forms of angiotensinogen (Ao-1 and Ao-2) that can be found in single animals in a distinct ratio. The ratio of Ao-1 to Ao-2 was determined by separation of Ao-1 and Ao-2 from 1 ml of plasma from individual rats on an SP-Sephadex C-50 column. Plasma from rats of three different strains, Wistar, Wistar-Kyoto (WKY), and spontaneously hypertensive rats (SHR), was investigated. In Wistar rats native plasma contained Ao-1 and Ao-2 in a ratio of 2.6:1. Twenty-four hours after nephrectomy, which increased the total Ao content 4.1-fold, this ratio was changed to 1.1:1. In native WKY and SHR the ratio of the two forms was similar to that in Wistar rats: 2.4:1 and 2.8:1, respectively. After nephrectomy the ratio of Ao-1 to Ao-2 was changed to 1.1:1 and 0.78:1 in WKY and SHR, respectively, while the total Ao content increased 4.9-fold and 8.2-fold in the two strains. Endogenous plasma renin inactivated the two forms of Ao, with a Km of 4.0 +/- 0.46 and 3.7 +/- 0.43 microM and a Vmax of 176 +/- 15.5 and 155 +/- 12.7 nM/hr, respectively. These results suggest that 1) Ao-1 and Ao-2 are synthesized in equimolar amounts, 2) the clearance of Ao-2 is faster than that of Ao-1 in control rats, and 3) under conditions of stimulated synthesis (i.e., after nephrectomy), the plasma content of Ao-2 increases faster than that of the more highly glycosylated form, Ao-1.

Differences in pattern of plasma angiotensinogen in native and nephrectomized rats.