Adipose tissue is an important source of angiotensinogen (AT) after liver. Since an association exists between body mass index, hypertension, and insulin-resistance, the role of insulin on the regulation of AT gene expression and AT secretion was examined in cultured Ob1771 and 3T3-F442A adipose cells. Within a physiological range of concentrations (1-17 nM), insulin exerted a negative effect on the abundance of AT mRNA and the secretion of AT. Alterations of insulin-resistance by treatment of adipose cells with TNF-alpha or the thiazolidinedione BRL49653 led respectively to a decrease or an increase in the potency of insulin to down-regulate AT gene expression, whereas maximal inhibition by insulin increased from 30% in TNFalpha-treated cells to 60% in BRL49653-treated cells. These results suggest that a potential link between insulin resistance and high blood pressure may exist by means of increased AT secretion from adipose tissue, especially in obese subjects.