Estrogen increases angiotensin II-induced c-Fos expression in the vasopressinergic neurons of the paraventricular nucleus in the female rat.

Previous studies in female rats have shown that estrogen treatment attenuates angiotensin II (AngII)-induced water intake. The mechanism underlying this attenuation may be decreased responsiveness to AngII, as revealed by a reduction in AngII binding to the angiotensin type 1 (AT1) receptor in the subfornical organ (SFO). It has not been determined whether these changes in receptor binding translate into changes in neuronal activity that, in turn, may influence behavior. Therefore, an estrogen-modulated change in neuronal pathways relevant to AngII-induced water intake was tested in ovariectomized (OVX) female rats using immunohistochemistry for the immediate early gene c-Fos as a marker for neuronal activation. Third cerebroventricular injection of AngII (6 ng) induced intense c-Fos immunoreactivity in forebrain regions associated with fluid intake, including the organum vasculosum of the lamina terminalis, the median preoptic nucleus, the SFO, the supraoptic nucleus and the paraventricular nucleus (PVN). Forty-eight-hour estradiol (10 microg) administration to OVX female rats increased AngII-induced c-Fos labeling in the lateral magnocellular neurons of the PVN by 30% as compared to vehicle-treated controls. Double labeling neurons in the PVN with c-Fos and either vasopressin or oxytocin antisera revealed that estrogen increased AngII-induced c-Fos expression by 28%, specifically in vasopressinergic neurons. Such changes in neuronal activation may explain the estrogen modulation of AngII-induced water intake that has been previously reported; it may be due to increased water retention to maintain plasma osmolality or to induction of a pressor response.