Mineralocorticoid treatment attenuates activation of oxytocinergic and vasopressinergic neurons by icv ANG II.
Central oxytocin (OT) neurons limit intracerebroventricular (icv) ANG II-induced NaCl intake. Because mineralocorticoids synergistically increase ANG II-induced NaCl intake, we hypothesized that mineralocorticoids may attenuate ANG II-induced activation of inhibitory OT neurons. To test this hypothesis, we determined the effect of deoxycorticosterone (DOCA; 2 mg/day) on icv ANG II-induced c-Fos immunoreactivity in OT and vasopressin (VP) neurons in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus and also on pituitary OT and VP secretion in male rats. DOCA significantly decreased the percentage of c-Fos-positive (%c-Fos+) OT neurons in the SON and PVN, both in the magnocellular and parvocellular subdivisions, and the %c-Fos+ VP neurons in the SON after a 5-ng icv injection of ANG II. DOCA also significantly reduced the %c-Fos+ OT neurons in the SON after 10 ng ANG II and tended to attenuate 10 ng ANG II-induced OT secretion. However, the %c-Fos+ OT neurons in DOCA-treated rats was greater after 10 ng ANG II, and DOCA did not affect the %c-Fos+ OT neurons in the PVN nor VP secretion or c-Fos immunoreactivity in either the SON or PVN after 10 ng ANG II. DOCA also did not significantly alter the effect of intraperitoneal (ip) cholecystokinin (62 microg) on %c-Fos+ OT neurons or of ip NaCl (2 ml of 2 M NaCl) on the %c-Fos+ OT and VP neurons. These findings indicate that DOCA attenuates the responsiveness of OT and VP neurons to ANG II without completely suppressing the activity of these neurons and, therefore, support the hypothesis that attenuation of OT neuronal activity is one mechanism by which mineralocorticoids enhance NaCl intake.
Roesch
D M
DM
Division of Endocrinology and Metabolism, Department of Medicine, Georgetown University, Washington, District of Columbia 20007, USA. roeschd@gunet.georgetown.edu
Blackburn-Munro
R E
RE
Verbalis
J G
JG
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004326:Drinking; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D010121:Oxytocin / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D013495:Supraoptic Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D014667:Vasopressins / Q000378:metabolism*
D016760:Proto-Oncogene Proteins c-fos; D014667:Vasopressins; D000804:Angiotensin II; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D010121:Oxytocin; D002766:Cholecystokinin