Mineralocorticoids and glucocorticoids cooperatively increase salt intake and angiotensin II receptor binding in rat brain.
Mineralocorticoids, such as deoxycorticosterone acetate (DOCA), and angiotensin II (AngII) act synergistically in the brain to elicit salt appetite. Glucocorticoids, such as dexamethasone (DEX), also may enhance the behavioral effects of DOCA and AngII. However, the brain regions involved in these behavioral interactions have not been elucidated. This study tested the hypothesis that DEX potentiates the effects of DOCA on AngII binding, especially at the AT1 receptor. We confirmed that DEX potentiated the effects of DOCA on salt appetite. Concomitantly, steroid-specific and region-specific changes in AT1 binding were noted. Specifically, in the hypothalamic paraventricular nucleus, treatment with DEX or DOCA + DEX increased AT1 binding. In the subfornical organ (SFO) and area postrema, there was an increase in AT1 binding when both steroids were combined, but not when given individually. However, there was no change in AT2 binding in any brain region studied and no change in AT1 or AT2 binding to either receptor subtype in the pituitary. The results indicate that DOCA and DEX may increase the sensitivity of the brain to the behavioral and physiological actions of AngII by upregulating AT1 receptors in the SFO and area postrema.
Shelat
S G
SG
Institute of Neurological Sciences, University of Pennsylvania, Philadelphia, Pa., USA.
King
J L
JL
Flanagan-Cato
L M
LM
Fluharty
S J
SJ
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D008901:Mineralocorticoids / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D012982:Sodium, Dietary
D005938:Glucocorticoids; D008901:Mineralocorticoids; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D012982:Sodium, Dietary; D000804:Angiotensin II