Key result
Angiotensinogen-deficient mice had significantly greater total densities of cardiac Ang II-R (31.1 vs 18.8 fmol/mg protein) and AT1-R compared to wild-type controls (P<.01).
Why the study?
Little is known about the regulation of cardiac angiotensin II type 1 and type 2 receptors by angiotensin II in vivo.
Absolute Event Rate: 31.1% vs 18.8%
p-value: p=<.01
Lack of circulating Ang II in angiotensinogen-deficient mice upregulates cardiac AT1 receptors, likely through translational or posttranslational mechanisms.
AT1-R upregulation without mRNA change in Ang II-deficient mice warrants caution in interpreting receptor dynamics; leaves open posttranslational mechanisms for human cardiac RAS.
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 with 125I-[Sar1,Ile8]-Ang II in plasma membrane fractions. AT1-R and AT2-R were distinguished using their specific antagonists CV-11974 and PD123319, respectively. Total densities of Ang II-R and AT1-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 AT2-R showed a slight but not significant increase in Atg-/- mice relative to Atg+/+ control animals. Kd 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 between Atg-/- and Atg+/+ mice. These results suggest that lack of Ang II may upregulate AT1-R through translational and/or posttranslational mechanisms in Atg-/- mice.
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Sumida et al. (1998) studied Angiotensinogen deficiency. Angiotensinogen deficiency (Atg-/-) vs. Atg+/+ mice was evaluated on Total densities of Ang II-R (fmol/mg protein) (p=<.01). Angiotensinogen-deficient mice had significantly greater total densities of cardiac Ang II-R (31.1 vs 18.8 fmol/mg protein) and AT1-R compared to wild-type controls (P<.01).
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