Increased Cardiac Angiotensin II Receptors in Angiotensinogen-Deficient Mice

—Two subtypes of angiotensin II (Ang II) receptors, type 1 (AT1 -R) and type 2 (AT2 -R), have been identified in the heart. However, little is known about the regulation of cardiac AT1 -R and AT2 -R by Ang II in vivo. Thus, we examined cardiac AT1 -R and AT2 -R in angiotensinogen-deficient (Atg-/- ) mice that are hypotensive and lack circulating Ang II. Cardiac Ang II receptors (Ang II-R) were assessed by radioligand binding with125 I-[Sar1 ,Ile8 ]–Ang II in plasma membrane fractions. AT1 -R and AT2 -R were distinguished using their specific antagonists CV-11974 andPD123319 , respectively. Total densities of Ang II-R and AT1 -R density were significantly greater in theAtg-/- mice thanAtg+/+ mice (31.1±2.8 versus18.8±2.1, 28.7±3.0 versus16.9±2.3 fmol/mg protein,P <.01, respectively), and AT2 -R showed a slight but not significant increase inAtg-/- mice relative toAtg+/+ control animals.K d values were not different between the two groups. In contrast to binding experiments, levels of Ang II type 1a receptor (AT1a -R) and AT2 -R mRNA did not differ betweenAtg-/- andAtg+/+ mice. These results suggest that lack of Ang II may upregulate AT1 -R through translational and/or posttranslational mechanisms inAtg-/- mice.