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Production of angiotensin within the SFO is sufficient to increase ERK1/2 and CREB activity in the SFO and PVN
Author(s) -
Coble Jeffrey,
Grobe Justin,
Cassell Martin,
Sigmund Curt D
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1165.11
Subject(s) - medicine , endocrinology , appetite , angiotensin ii , creb , chemistry , sodium , renin–angiotensin system , vasopressin , biology , receptor , biochemistry , organic chemistry , gene , transcription factor , blood pressure
Release of angiotensin II (ANG) within the brain increases fluid intake and sodium appetite. We sought to determine the sufficiency of ANG production in the subfornical organ (SFO) to increase fluid intake and sodium appetite by breeding mice expressing human renin under the neuron specific promoter, synapsin (sR), with mice expressing a conditionally inducible human AGT (hAGT) construct (A Red ; double transgenic sRA Red ). Injection of adenovirus encoding Cre‐recombinase (AdCRE) into the lateral ventricle (ICV) of sRA Red mice significantly increases hAGT transcript production within the SFO compared to other cardiovascular brain regions (p<0.05, n=12). One month after ICV AdCRE in sRA Red mice total fluid intake and sodium appetite (0.436±0.04 mL/g/day; 1.721±0.087 mEq/day) increased compared to littermate controls (0.176±0.04 mL/g/day, P<0.001; 1.257 mEq/day, p<0.05; n=6) in a two‐bottle choice paradigm (water vs. 0.3M NaCl). After ICV AdCRE we observed a relative increase in immunostaining for ERK1/2 and CREB, but not p‐38 MAPK activity in the SFO and paraventricular nucleus (PVN) of sRA Red compared to littermate controls. In conclusion, we demonstrate that activation of ANG production specifically in the SFO is sufficient to increase ERK1/2 and CREB activity in the SFO and PVN, and to increase total fluid intake and sodium appetite.