Interaction of glucocorticoids and interleukins in the control of hypothalamic neurohypophysial system output in salt loaded male rats

The present study investigated the effects of a 4-day salt load (0.3 M NaCl, SL) and dexamethasone treatment (DEXA, 1 mg/Kg, subcutaneous) on the mechanisms possibly underlying glucocorticoid-mediated effects on hypothalamic neurohypophyseal system (HNS) activity. As expected, SL animals developed hyperosmolality, reflecting the progressive increase in plasma sodium concentrations. SL also triggered increased hypothalamic expression of vasopressin (AVP) and oxytocin (OT) messenger RNAs (mRNAs), increased magnocellular neuronal activation, and enhanced plasma hormone concentrations. Plasma corticosterone, interleukin (IL) 1β and tumor necrosis factor alfa, but not IL-6 levels, were also elevated in response to SL. Increased salt consumption also significantly decreased hypothalamic mRNA expression for the p65 subunit of the nuclear factor kappa B (NFkB), and increased mRNA expression for type β NFkB inhibitory protein (IκBβ). The protein expression ratio between phosphorylated and total NFκB was also elevated in SL rats. DEXA administration, in turn, prevented SL-induced AVP and OT release, as well as decreased corticosterone/IL plasma levels. Therefore, the present results suggest that increased salt consumption may originate a systemic-driven pro-inflammatory response, which can contribute to the increased secretion of corticosterone observed in SL animals. We therefore hypothesize that elevated systemic IL levels, in parallel with corticosterone secretion, may constitute, besides hyperosmolality, important redundant stimuli triggering SL-induced neuropeptide release. Conversely, high levels of corticosterone would produce, in the long term, inhibition of HNS activity and the termination of the neurosecretory response.