Linked Life Data

11509454

Source:http://linkedlifedata.com/resource/pubmed/id/11509454

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-8-17
pubmed:abstractText
In addition to the circulatory renin (REN)-angiotensin system (RAS), a tissue RAS having an important role in cardiovascular function also exists in the central nervous system. In the brain, angiotensinogen (AGT) is expressed in astrocytes and in some neurons important to cardiovascular control, but its functional role remains undefined. We generated a transgenic mouse encoding the human AGT (hAGT) gene under the control of the human glial fibrillary acidic protein (GFAP) promoter to experimentally dissect the role of brain versus systemically derived AGT. This promoter targets expression of transgene products to astrocytes, the most abundant cell type expressing AGT in brain. All transgenic lines exhibited hAGT mRNA expression in brain, with variable expression in other tissues. In one line examined in detail, transgene expression was high in brain and low in tissues outside the central nervous system, and the level of plasma hAGT was not elevated over baseline. In the brain, hAGT protein was mainly localized in astrocytes, but was present in neurons in the subfornical organ. Intracerebroventricular (ICV) injection of human REN (hREN) in conscious unrestrained mice elicited a pressor response, which was abolished by ICV preinjection of losartan. Double-transgenic mice expressing the hREN gene and the GFAP-hAGT transgene exhibited a 15-mm Hg increase in blood pressure and an increased preference for salt. Blood pressure in the hREN/GFAP-hAGT mice was lowered after ICV, but not intravenous losartan. These studies suggest that AGT synthesis in the brain has an important role in the regulation of blood pressure and electrolyte balance.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
365-72
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11509454-Angiotensinogen, pubmed-meshheading:11509454-Animals, pubmed-meshheading:11509454-Astrocytes, pubmed-meshheading:11509454-Blood Pressure, pubmed-meshheading:11509454-Brain, pubmed-meshheading:11509454-Dose-Response Relationship, Drug, pubmed-meshheading:11509454-Drinking, pubmed-meshheading:11509454-Gene Expression, pubmed-meshheading:11509454-Glial Fibrillary Acidic Protein, pubmed-meshheading:11509454-Humans, pubmed-meshheading:11509454-Hypertension, pubmed-meshheading:11509454-Injections, Intravenous, pubmed-meshheading:11509454-Injections, Intraventricular, pubmed-meshheading:11509454-Losartan, pubmed-meshheading:11509454-Mice, pubmed-meshheading:11509454-Mice, Transgenic, pubmed-meshheading:11509454-Neurons, pubmed-meshheading:11509454-Organ Specificity, pubmed-meshheading:11509454-Promoter Regions, Genetic, pubmed-meshheading:11509454-RNA, Messenger, pubmed-meshheading:11509454-Renin, pubmed-meshheading:11509454-Subfornical Organ, pubmed-meshheading:11509454-Transgenes, pubmed-meshheading:11509454-Water-Electrolyte Balance
pubmed:year
2001
pubmed:articleTitle
Elevated blood pressure in transgenic mice with brain-specific expression of human angiotensinogen driven by the glial fibrillary acidic protein promoter.
pubmed:affiliation
Department of Internal Medicine and Physiology & Biophysics, University of Iowa, Iowa City, Iowa 52242, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't