MORIMOTO Satoshi
   Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine
   Position   Associate Professor
Article types Original article
Language English
Peer review Peer reviewed
Title The brain renin-angiotensin system in transgenic mice carrying a highly regulated human renin transgene.
Journal Formal name:Circulation research
Abbreviation:Circ Res
ISSN code:15244571/00097330
Domestic / ForeginForegin
Volume, Issue, Page 90(1),pp.80-6
Author and coauthor Morimoto Satoshi†, Cassell Martin D, Sigmund Curt D
Authorship Lead author
Publication date 2002/01
Summary We previously reported the generation of 2 novel transgenic mouse models containing the human renin (hREN) gene encoded on P1 artificial chromosomes (PAC) containing large amounts of 5'-flanking DNA. These mice exhibit a very narrow tissue-specific expression profile and exhibit tightly regulated expression in kidney in response to physiological cues. In brain, transcription of hREN occurs from an alternative upstream promoter, causing translation to initiate within exon-II and potentially generating an intracellular form of active renin. Double transgenic mice containing a PAC transgene and the human angiotensinogen (hAGT) gene (P+/A+) are moderately hypertensive. We tested whether increased RAS activity in the brain contributes to the mechanism of hypertension in P+/A+ double transgenic mice. Expression of hREN mRNA in brain was confirmed in 4 independent PAC transgenic lines and utilization of the alternative transcription start site in brain was confirmed in each line. Human REN immunostaining was observed in the dorsal cochlear nucleus, hypothalamus, and cortex. P+/A+ mice exhibited a greater fall in mean arterial pressure after intracerebroventricular injection of losartan than controls. P+/A+ mice exhibited a greater drop in arterial pressure after intravenous injection of a vasopressin V(1) receptor antagonist, and an equivalent drop in arterial pressure after intravenous injection of a ganglion blocker compared with controls. These results support the hypothesis that renin is endogenously expressed in the brain and suggest that increased brain RAS activity may contribute to the maintenance of moderate hypertension in P+/A+ transgenic mice at least in part by a vasopressin-dependent mechanism.
DOI 10.1161/hh0102.102272
PMID 11786522