Shinichiro Nishimatsu
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of Natural Sciences,
   Position   Professor
Article types 原著
Language English
Peer review Peer reviewed
Title Angiotensin II type 1a receptor-deficient mice with hypotension and hyperreninemia.
Journal Formal name:The Journal of biological chemistry
Abbreviation:J Biol Chem
ISSN code:00219258/1083351X
Volume, Issue, Page 270(32),pp.18719-18722
Author and coauthor Sugaya Takeshi, Nishimatsu Shin-ichiro, Tanimoto Keiji, Takimoto Eriko, Yamagishi Toshiyuki, Imamura Kenkichi, Goto Saori, Imaizumi Kazunori, Hisada Yutaka, Otsuka Akio, Uchida Hiromi, Sugiura Masaki, Fukuta Katsuhiro, Fukamizu Akiyoshi, Murakami Kazuo
Authorship 2nd author
Publication date 1995/08
Summary Angiotensin (AT) II, the bioactive octapeptide in the renin-angiotensin system that plays a key role in cardiovascular homeostasis, exerts its multiple effects through the different types of AT receptors, AT1a, AT1b, and AT2. Previously, we showed chronic hypotension in angiotensinogen (the precursor of AT)-deficient mice and a dramatic increase in renin mRNA levels in its kidney, but it remains unclear which types of AT receptors regulate the blood pressure and renin gene expression. In order to elucidate the physiological roles of AT1a receptor, we generated mutant mice with a targeted replacement of the AT1a receptor loci by the lacZ gene. In the heterozygous mutant mice, the strong lacZ staining was found in the glomerulus and juxtaglomerular apparatus of the renal cortex, which coincided with that of the signals detected by in situ hybridization. Chronic hypotension was observed in the heterozygous and homozygous mutant mice, with 10 and 22 mm Hg lower systolic blood pressure, respectively, than that of wild-type littermates. Both the levels of renin mRNA in the kidney and plasma renin activity were markedly increased only in the homozygous mutant mice. These results demonstrated that an AT1a-mediated signal transduction pathway is, at least in part, involved in the regulation of blood pressure and renin gene expression.
DOI 10.1074/jbc.270.32.18719
Document No. 7642517