Renin-angiotensin system in hypertension
The renin-angiotensin system (RAS) is one of the determinant factors in regulating blood pressure and sodium absorption. RAS has been shown to accelerate various diseases such as renal failure, atherosclerosis, cardiac hypertrophy, and pulmonary hypertension. The reaction between renin, produced in the kidney, and its substrate angiotensinogen, produced in the liver, is the initial and rate-limiting step in the enzymatic cascade that generates angiotensin I. Angiotensin-converting enzyme in the lung converts angiotensin I to the potent vasoconstrictor angiotensin II (Ang II).
The depositor reported that overactivation of the RAS induces hypertension in the F1 generation obtained from breeding between a female carrying the human renin gene (hRN+/+) and a male possessing the human angiotensinogen gene (hAG+/+) [1-3]. Moreover, female hAG+/+ mice when bred with male hRN+/+ mice are hypertensive specifically in late pregnancy [4,5], suggesting possible implications for preeclampsia or pregnancy-induced hypertension, a life-threatening disorder for human mothers and fetuses. hRN+/+ and hANG+/+ mice provide the opportunity to understand the role of the RAS in hypertension and other common diseases.
Related strain : (hRN8-12 x hAG2-5)F1 RBRC02432
|Depositor||:||Dr. Akiyoshi Fukamizu
Graduate School of Life and Environmental Sciences, University of Tsukuba
|References||:||Fukamizu A, Seo MS, Hatae T, Yokoyama M, Nomura T, Katsuki M, Murakami K. Tissue-specific expression of the human renin gene in transgenic mice. Biochem Biophys Res Commun; 165(2):826-32, 1989.
Takahashi S, Fukamizu A, Hasegawa T, Yokoyama M, Nomura T, Katsuki M, Murakami K. Expression of the human angiotensinogen gene in transgenic mice and transfected cells. Biochem Biophys Res Commun; 180(2):1103-9, 1991.
Fukamizu A, Sugimura K, Takimoto E, Sugiyama F, Seo MS, Takahashi S, Hatae T, Kajiwara N, Yagami K, Murakami K. Chimeric renin-angiotensin system demonstrates sustained increase in blood pressure of transgenic mice carrying both human renin and human angiotensinogen genes. J. Biol. Chem; 268(16): 11617-21, 1993.
Takimoto E, Ishida J, Sugiyama F, Horiguchi H, Murakami K, Fukamizu A. Hypertension induced in pregnant mice by placental renin and maternal angiotensinogen. Science; 274(5289):995-8, 1996.
Ishida J, Matsuoka T, Saito-Fujita T, Inaba S, Kunita S, Sugiyama F, Yagami K, Fukamizu A. Pregnancy-associated homeostasis and dysregulation: lessons from genetically modified animal models. J Biochem; 150(1):5-14, 2011.