Clearance from circulation and organ distribution of 125I-endothelin-1 in carbon tetrachloride-induced acute liver injury and hepatic fibrosis rats

Objectives: To verify whether endothelin (ET) ETB receptors are involved in removal of circulating ET-1, and to examine whether acute liver injury (ALI) and hepatic fibrosis (HF) affect the removal rate and organ distribution of ET-1. Methods: ALI and HF rats were made by single and repeated injection of carbon tetrachloride, respectively. Under ketamine anesthesia, 125I-ET-1 was i.v. bolus injected, then blood samples were collected as scheduled (1, 2, 5, 10, 15 and 30 min after injection). The lungs, liver, kidneys, and aorta were harvested to measure the accumulated radioactivity. Normal control (NC) rats and BQ788-pretreated (BQ) rats also underwent the same injection and sampling procedure. 125I-ET-1 binding sites in the liver were studied with lightmicroscopic autoradiography. Results: BQ788 substantially decreased the removal rate of 125 I-ET-1 from circulation and tended to decrease the lung trapping of the tracer, while significantly increased the hepatic distribution of the tracer. Removal of 125IET-1 from systemic circulation was impaired both in ALI and HF rats. 125I-ET-1 distribution was reduced in the liver and kidneys of ALI, whereas increased in the lungs of both ALI and HF. Light-microscopic autoradiography revealed a dense distribution of grains in the periportal areas of NC and ALI rats, but such gradient was lost in HF rats. Conclusions: We confirmed the physiology for removal from circulation and organ trapping of ET-1. The decreased ET-1 removal from circulation may be due to reductions in hepatic and renal degradation of ET-1 in ALI rats, and may be ascribed to anatomical and/or functional diminution of lipocytes in the cirrhotic liver.