Increased Cardiac Angiotensin II Receptors in Angiotensinogen-Deficient Mice

Autor: Machiko Yabana, Masao Ishii, Shunichi Kobayashi, Kazuo Murakami, Satoshi Umemura, Nobuo Nyui, Hitoshi Miyazaki, Akiyoshi Fukamizu, Tomoaki Ishigami, Kouichi Tamura, Minoru Kihara, Hisao Ochiai, Yoichi Sumida
Rok vydání: 1998
Předmět:
Zdroj: Hypertension. 31:45-49
ISSN: 1524-4563
0194-911X
Popis: Abstract —Two subtypes of angiotensin II (Ang II) receptors, type 1 (AT 1 -R) and 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 II in vivo. Thus, we examined cardiac AT 1 -R and AT 2 -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 125 I-[Sar 1 ,Ile 8 ]–Ang II in plasma membrane fractions. AT 1 -R and AT 2 -R were distinguished using their specific antagonists CV-11974 and PD123319 , respectively. Total densities of Ang II-R and AT 1 -R density were significantly greater in the Atg-/- mice than Atg+/+ mice (31.1±2.8 versus18.8±2.1, 28.7±3.0 versus16.9±2.3 fmol/mg protein, P 2 -R showed a slight but not significant increase in Atg-/- mice relative to Atg+/+ control animals. K d values were not different between the two groups. In contrast to binding experiments, levels of Ang II type 1a receptor (AT 1a -R) and AT 2 -R mRNA did not differ between Atg-/- and Atg+/+ mice. These results suggest that lack of Ang II may upregulate AT 1 -R through translational and/or posttranslational mechanisms in Atg-/- mice.
Databáze: OpenAIRE