[Angiotensinogen: gene expression and protein localization in human tissues].

Angiotensinogen, the precursor of the biologically active peptide angiotensin II, is known to be synthesized in the liver and to be localized in plasma, constituting the circulating renin-angiotensin (R-A) system. Recent animal studies have provided evidence for the local generation of angiotensinogen within tissues, independently of the circulating R-A system. To determine the sites of angiotensinogen synthesis in human tissues, we tested for the presence of angiotensinogen and its mRNA in various organs. Messenger RNAs extracted from the liver, kidneys, heart, and brain were all hybridized with human-angiotensinogen complementary DNA. By using a monoclonal antibody generated by in vitro immunization of spleen cells with the synthetic peptide, we first confirmed that the antibody detected only angiotensinogen on immunoblots. In immunohistochemical studies, intense immunoreactivity was found in atrial muscle and in the muscle fibers of the conduction system. The ventricular working myocytes were not stained. Less intense staining was observed in the glomerular tufts of the kidneys, in a few hepatocytes and Kupffer cells, and in the bile duct epithelium of the liver. Thus we demonstrated that angiotensinogen is also synthesized in extrahepatic tissues, including the heart, and that it is localized mainly in the specific cells of the heart. This suggests that the tissue R-A system plays an important role in the human heart.