Half-life of rat angiotensinogen: influence of nephrectomy and lipopolysaccharide stimulation.
The in vivo half-life of two differently glycosylated subforms of rat angiotensinogen (Ao), Ao-1 and Ao-2, was studied in native and nephrectomized rats, as well as in rats treated with lipopolysaccharides (LPS). The metabolic clearance rate of both 125I-labeled derivatives fits a two-compartment model using a non-linear curve fitting program (SCTFIT). Both forms show an initial rapid phase with a half-life of about 1 h. This clearance rate was not altered by either nephrectomy or LPS administration. In the intact rat the two forms were eliminated with a second slower phase half-life of 8.07 h (Ao-1) and 4.53 h (Ao-2), respectively. Following nephrectomy, in the absence of renin, the slower phase of clearance of both forms decreased (t1/2 Ao-1:9.77 h; t1/2 Ao-2: 10.50 h). Induction of low renin concentrations by LPS administration decreased the half-life of the more highly glycosylated form Ao-1 (t1/2: 6.93 h), while that of Ao-2 increased (t1/2: 5.07 h). Inactive angiotensinogen, des-AngI-Ao, of both forms demonstrated a faster metabolic clearance rate in native rats than that of the intact glycoproteins (t1/2 Ao-1: 5.68 h; t1/2 Ao-2: 3.97 h). Based on the plasma levels of these two angiotensinogen subtypes in normal rats, these data suggest a higher secretion rate by the liver for the more highly glycosylated form Ao-1 and a slower clearance rate by the kidney. In contrast, the less glycosylated form shows more rapid elimination by the kidney. Following nephrectomy both glycoproteins are secreted and eliminated in an equimolar ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
Hilgenfeldt
U
U
Department of Pharmacology, University of Heidelberg, F.R.G.
D000808:Angiotensinogen / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006031:Glycosylation; D006207:Half-Life; D007457:Iodine Radioisotopes; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009392:Nephrectomy; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D007457:Iodine Radioisotopes; D008070:Lipopolysaccharides; D000808:Angiotensinogen