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Adrenal hormones are necessary for the hydromineral phenotypes of transgenic mice with central renin‐angiotensin system overactivity
Author(s) -
Grobe Justin L.,
Grobe Connie L.,
Rocha Borges Giulianna,
Beltz Terry A.,
Johnson Alan K.,
Sigmund Curt D.
Publication year - 2009
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.23.1_supplement.967.2
Subject(s) - endocrinology , medicine , polyuria , polydipsia , renin–angiotensin system , appetite , angiotensin ii , hormone , chemistry , adrenalectomy , homeostasis , blood pressure , diabetes mellitus
To examine the roles of the central renin‐angiotensin system (RAS) in blood pressure and fluid volume homeostasis, our lab previously developed the sRA mouse model, in which human renin is expressed via the neuron‐specific synapsin promoter, and human angiotensinogen via its endogenous promoter. Due to species‐specificity of this reaction, RAS overactivity is restricted to the brain. sRA mice exhibit polydipsia (control, 0.04±0.01 vs sRA, 0.31±0.12 mL/g/d), polyuria (0.08±0.02 vs 0.92±0.04 g/g/d), and a robust sodium appetite (0.94±0.18 vs 3.93±0.07 mEq/d). Here, we examined whether elevated HPA‐axis activity is necessary for these phenotypes. Four weeks after total adrenalectomy, the sodium appetite of sRA mice was completely normalized (0.72±0.21 mEq/d), and the polydipsia (0.11±0.01 mL/g/d) and polyuria (0.15±0.01 g/g/d) were significantly attenuated. In a separate cohort, acute spironolactone treatment partially blocked the sodium intake of sRA mice (3.03±0.31 down to 2.33±0.44 mEq/d), suggesting the involvement of multiple adrenal hormones in this behavior. From these data, we conclude that multiple adrenal hormones are necessary for the dipsogenic and sodium appetite behaviors of mice with chronic overactivity of the brain RAS. Ongoing work is dissecting the contribution of glucocorticoids in hydromineral regulation in sRA mice. (JLG supported by the APS; CLG, AKJ, CDS supported by NIH)