Genetic deletion of AT2 receptor antagonizes angiotensin II-induced apoptosis in fibroblasts of the mouse embryo

To examine whether angiotensin II (Ang II) can trigger apoptosis via Ang II type 2 (AT2) receptor, two genotypes of skin fibroblasts cultured from the AT2 receptor gene targeting homozygous (AT2-/-) and wild-type (AT2+/+) mouse embryos, respectively, were studied when exposed to Ang II. In the AT2+/+ fibroblasts, mRNA expression of the AT2 receptor was modulated by Ang II in a dose-dependent manner and apoptosis appeared with the convincing features of internucleosomal DNA fragmentation and DNA content decrease after stimulation with Ang II, whereas Ang II had no significant impact on the AT2-/- fibroblasts due to the AT2 receptor gene deletion. This is the first report using a gene targeting study to demonstrate that Ang II induces apoptosis through the AT2 receptor in the fibroblasts of the mouse embryo. (C) 1998 Academic Press.