title: Increased cardiac angiotensin II receptors in angiotensinogen-deficient mice.
abstract: 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.
authors.affiliation: Second Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sumida
authors.forename: S
authors.initials: S
authors.lastname: Umemura
authors.forename: K
authors.initials: K
authors.lastname: Tamura
authors.forename: M
authors.initials: M
authors.lastname: Kihara
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Ishigami
authors.forename: M
authors.initials: M
authors.lastname: Yabana
authors.forename: N
authors.initials: N
authors.lastname: Nyui
authors.forename: H
authors.initials: H
authors.lastname: Ochiai
authors.forename: A
authors.initials: A
authors.lastname: Fukamizu
authors.forename: H
authors.initials: H
authors.lastname: Miyazaki
authors.forename: K
authors.initials: K
authors.lastname: Murakami
authors.forename: M
authors.initials: M
authors.lastname: Ishii
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000808:Angiotensinogen / Q000172:deficiency*; D000818:Animals; D015152:Blotting, Northern; D007022:Hypotension; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000737:chemistry*; D009924:Organ Culture Techniques; D011869:Radioligand Assay; D011945:Receptors, Angiotensin / Q000032:analysis* / Q000145:classification / Q000378:metabolism
chemical_list: D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D000804:Angiotensin II