Journal article
Evidence Supporting a Functional Role for Intracellular Renin in the Brain
Hypertension (Dallas, Tex. 1979), Vol.47(3), pp.461-466
03/2006
DOI: 10.1161/01.HYP.0000203308.52919.dc
PMID: 16446393
Abstract
The brain renin–angiotensin system is implicated in the regulation of blood pressure (BP) and fluid homeostasis. Recent studies reveal that 2 forms of renin are expressed in the brain of rodents and humanssecreted prorenin and a nonsecreted intracellular form of active renin (icREN). Although the intracellular action of renin has long been postulated, no data supporting its role in BP regulation has been reported. Therefore, we directly evaluated whether this form of renin has physiological implications for BP regulation by characterizing transgenic mice expressing human icREN driven by the glial fibrillary acidic protein (GFAP) promoter and comparing it with similar mice expressing the secreted form of renin. GFAP-icREN mice express hREN primarily in the brain and at the same level of expression as GFAP-secreted prorenin. Unlike the secreted form, which can be detected in cerebrospinal fluid, no human renin could be detected in the cerebrospinal fluid of GFAP-icREN mice. GFAP-icREN mice were then bred with transgenic mice expressing human angiotensinogen, also driven by the GFAP promoter. Double-transgenic mice expressing either the intracellular renin (2.0±0.12 mL/10 g/day) or secreted renin (2.8±0.3 mL/10 g/day) exhibited an increase in drinking volume compared with nontransgenic littermates (1.5±0.1 mL/10 g/day). Both models exhibited an increase in mean arterial pressure (137±5 and 133±8 mm Hg, respectively) compared with control littermates (115±3 mm Hg), which could be rapidly reduced after ICV injection of losartan. These data support the concept of an intracellular form of renin in the brain, which may provoke functional changes in fluid homeostasis and BP regulation.
Details
- Title: Subtitle
- Evidence Supporting a Functional Role for Intracellular Renin in the Brain
- Creators
- Julie Lavoie - From the Departments of Internal Medicine and Physiology and Biophysics (J.L.L., X.L., R.A.B., C.D.S.) and Psychology (T.G.B., A.K.J.), University of Iowa, Iowa City, IowaXuebo LiuRobert BiancoTerry BeltzAlan JohnsonCurt Sigmund
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.47(3), pp.461-466
- DOI
- 10.1161/01.HYP.0000203308.52919.dc
- PMID
- 16446393
- NLM abbreviation
- Hypertension
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Publisher
- American Heart Association, Inc
- Language
- English
- Date published
- 03/2006
- Academic Unit
- Molecular Physiology and Biophysics; Psychological and Brain Sciences; Neuroscience and Pharmacology; Health, Sport, and Human Physiology
- Record Identifier
- 9984213425902771
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