Angiotensin II accelerates mammary gland development independently of high blood pressure in pregnancy-associated hypertensive mice.
Angiotensin II (AngII) is a vasopressor hormone that has critical roles in maintenance of normal blood pressure and pathogenesis of cardiovascular diseases. We previously generated pregnancy-associated hypertensive (PAH) mice by mating female human angiotensinogen transgenic mice with male human renin transgenic mice. PAH mice exhibit hypertension in late pregnancy by overproducing AngII. A recent study demonstrated that angiotensin II type I (AT1) receptor is expressed in mammary epithelial cells and its signaling is critical for mammary gland involution after weaning. However, the role of AngII-AT1 receptor signaling in the development of mammary gland during pregnancy remains unclear. In this study, to investigate the role of AngII-AT1 receptor signaling in mammary gland development during pregnancy, we analyzed the mammary gland of PAH mice. Histological and gene expression analyses revealed that lobuloalveolar development was accelerated with increased milk protein production and lipid accumulation in the mammary gland of PAH mice. Furthermore, AT1 receptor blocker treatment suppressed acceleration of mammary gland development in PAH mice, while the treatment of hydralazine, another antihypertensive drug, did not. These data suggest that AngII-AT1 receptor-induced signaling accelerates mammary gland development during pregnancy through hypertension-independent mechanism.
Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Kazuya
K
Murata
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Altansarnai
A
Baasanjav
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Chulwon
C
Kwon
Ph.D. Program in Human Biology, School of Integrative Global Majors (SIGMA), University of Tsukuba, Tsukuba, Ibaraki, Japan.
Misuzu
M
Hashimoto
Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki, Japan Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Junji
J
Ishida
Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki, Japan Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan akif@tara.tsukuba.ac.jp.
Akiyoshi
A
Fukamizu
Angiotensin II; hypertension; mammary gland development; pregnancy