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 Neuron-specific expression of human angiotensinogen in brain causes increased salt appetite.
Journal Formal name：Physiological genomics
Abbreviation：Physiol Genomics
ISSN code：15312267/10948341
Domestic / ForeginForegin
Volume, Issue, Page 9(2),pp.113-20
Author and coauthor Morimoto Satoshi†, Cassell Martin D, Sigmund Curt D
Authorship Lead author
Publication date 2002
Summary The brain renin-angiotensin system (RAS) has an important role in the regulation of cardiovascular function. In the brain, angiotensinogen (AGT) is expressed mainly in astrocytes (glia) and in some neurons in regions controlling cardiovascular activities. Because of the inability to dissect the functional role of astrocyte- vs. neuron-derived AGT in vivo by pharmacological approaches, the exact role of neuron-derived AGT in the regulation of blood pressure (BP) and fluid and electrolyte balance remains unclear. Therefore, we generated a transgenic mouse model overexpressing human AGT under the control of a neuron-specific (synapsin I) promoter (SYN-hAGT). These mice exhibited high-level expression of human AGT mRNA in the brain, with lower expression in the kidney and heart. Human AGT was not detected in plasma, but in the brain it was expressed exclusively in neurons. Intracerebroventricular (30 ng) but not intravenous (500 ng) injection of purified human renin (hREN) caused a pressor response, which was prevented by intracerebroventricular preinjection of the angiotensin II type 1 receptor antagonist losartan, indicating an AT(1) receptor-dependent functional role of neuron-derived AGT in the regulation of BP in response to exogenous REN. Double transgenic mice expressing both the hREN gene and SYN-hAGT transgene exhibited normal BP and water intake but had an increased preference for salt. These data suggest that neuronal AGT may play an important role in regulating salt intake and salt appetite.
DOI 10.1152/physiolgenomics.00007.2002
PMID 12006677