INCREASED CARDIAC ANGIOTENSIN-II RECEPTORS IN ANGIOTENSINOGEN-DEFICIENT MICE

Two subtypes of angiotensin II (Ang II) receptors, type 1 (AT(1)-R) an d type 2 (AT(2)-R), have been identified in the heart. However, little is known about the regulation of cardiac AT(1)-R and AT(2)-R by Ang I I in vivo. Thus, we examined cardiac AT(1)-R and AT(2)-R in angiotensi nogen-deficient (Atg-/-) mice that are hypotensive and lack circulatin g Ang II. Cardiac Ang II receptors (Ang II-R) were assessed by radioli gand binding with I-125-[Sar(1),Ile(8)]-Ang II in plasma membrane frac tions. AT(1)-R and AT(2)-R were distinguished using their specific ant agonists CV-11974 and PD123319, respectively. Total densities of Ang I I-R and AT(1)-R density were significantly greater in the Atg-/- mice than Atg+/+ mice (31.1+/-2.8 versus 18.8+/-2.1, 28.7+/-3.0 versus 16.9 +/-2.3 fmol/mg protein, P<.01, respectively), and AT(2)-R showed a sli ght bur not significant increase in Atg-/- mice relative to Atg+/- con trol animals. K-d values were not different between the two groups. In contrast to binding experiments, levels of Ang II type 1a receptor (A T(1a)-R) and AT(2)-R mRNA did not differ between Atg-/- and Atg+/+ mic e. These results suggest that lack of Ang II may upregulate AT(1)-R th rough translational and/or posttranslational mechanisms in Atg-/- mice .