Role of the kidney in the plasma clearance of angiotensinogen in the rat: Plasma clearance and tissue distribution of 125I-angiotensinogen

Abstract

We studied the tissue distribution and plasma clearance of angiotensinogen (AGN) in rats following an i.v. injection of 125I-labeled AGN. The plasma clearance rate of [ 125I]AGN fits a two-compartment model with half-lives of 10.2 ± 1.5 min and 4.1 ± 0.5 h in non-treated rats and the half-life of slower phase significantly increased to 10.2 ± 1.1 h following bilateral nephrectomy. Radioactivity was predominantly distributed in the kidneys (4.9%) and to a lesser extent in the liver (1.8%), testis (1.2%), spleen (0.61%), heart (0.35%), lung (0.18%), thymus (0.03%) and brain (0.03%). The subcellular distribution of radioactivity in the kidney was 64% in the soluble fraction and 33% in the crude mitochondrial-lysosomal fraction. Sodium dodecylsulfate-polyacrylamide gel electrophoresis revealed that the radioactivity in the soluble fraction consisted of proteins corresponding to intact [ 125I]AGN, whereas the mitochondrial-lysosomal fraction contained additional radioactive proteins with molecular weights between 18,000 and 29,000. When isolated kidney cells were incubated with [ 125I]AGN at 0 °C, the radioactive binding was saturable and specific with a Kd value of 4.8 × 10 −11M, whereas incubation at 37 °C resulted in the appearance of degraded products of [ 125I]AGN in the medium. These results suggested that circulating AGN is cleared mainly by the kidneys via receptor-mediated endocytosis, which may play an important role in regulating plasma level of AGN.