ROLE OF THE KIDNEY IN THE PLASMA-CLEARANCE OF ANGIOTENSINOGEN IN THE RAT - PLASMA-CLEARANCE AND TISSUE DISTRIBUTION OF I-125 ANGIOTENSINOGEN

We studied the tissue distribution and plasma clearance of angiotensin ogen (AGN) in rats following an i.v. injection of I-125-labeled AGN. T he plasma clearance rate of [I-125]AGN fits a two-compartment model wi th half-lives of 10.2 +/- 1.5 min and 4.1 +/- 0.5 h in non-treated rat s, and the half-life of slower phase significantly increased to 10.2 /- 1.1 h following bilateral nephrectomy. Radioactivity was predominan tly distributed in the kidneys (4.9%), and to a lesser extent in the l iver (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 r adioactivity in the kidney was 64% in the soluble fraction and 33% in the crude mitochondrial-lysosomal fraction. Sodium dodecylsulfate-poly acrylamide gel electrophoresis revealed that the radioactivity in the soluble fraction consisted of proteins corresponding to intact [I-125] 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 [I-125]AGN at 0 degre es C, the radioactive binding was saturable and specific with a Kd val ue of 4.8 X 10(-11)M, whereas incubation at 37 degrees C resulted in t he appearance of degraded products of [I-125]AGN in the medium. These results suggested that circulating AGN is cleared mainly by the kidney s via receptor-mediated endocytosis, which may play an important role in regulating plasma level of AGN.