Regulation of angiotensinogen production by angiotensin II analogues

Specific binding sites for angiotensin II (Ang II) were identified in a human hepatoma cell line, HepG2. Binding of [I]-Sar Ang II to these cells showed a high-affinity site with a Kd of 2.4 ± 0.2 nmol/l. This specific binding was not changed during the cell cycle and showed no alteration after 24 h of treatment with Sar-Ang II (10 mol/l). Exposure of HepG2 cells to the Ang II agonist Sar-Ang II caused a dose-dependent decrease in angiotensinogen production.The maximal inhibitory effect was at a dose of 10 mol/l Sar-Ang II which elicited 67% inhibition of angiotensinogen production after 24 h (control2.015 ± 0.5 μg angiotensinogen/mg DNA; Sar-Ang II 10 mol/l0.68 ± 0.03 μg angiotensinogen/mg DNA).Fifty per cent inhibition was obtained at a dose of 10 mol/l Sar-Ang II. Angiotensin II had a less marked effect, showing maximal inhibition of 40%. This study shows that the HepG2 cells possess specific Ang II binding sites and that Ang II analogues induce a dose-dependent inhibition of angiotensinogen production in cell culture.