Increased expression of the mineralocorticoid receptor in the brain of spontaneously hypertensive rats.

The mineralocorticoid receptor (MR) has been considered as both neuroprotective and damaging to the function of the central nervous system. MR may be also involved in central regulation of blood pressure. In the present study, we compared the expression of MR and the glucocorticoid receptor (GR) in the hippocampus and hypothalamus of 16-week-old spontaneously hypertensive rats (SHR) and normotensive control Wistar Kyoto (WKY) rats. In the hippocampus, MR expression was studied by in situ hybridization (ISH), quantitative polymerase chain reaction (PCR) and immunohistochemistry, whereas GR expression was analysed using the latter two procedures. Hypertensive animals showed an increased expression of MR mRNA in the whole hippocampus according to qPCR data and also in CA3 by ISH. Immunocytochemical staining for MR of the dorsal hippocampus, however, did not reveal differences between SHR and WKY rats. SHR showed elevated hypothalamic MR mRNA by qPCR, as well as an increased number of MR immunopositive cells in the magnocellular paraventricular region, compared to WKY rats. By contrast, expression levels of GR mRNA or protein in the hippocampus and hypothalamus of SHR were similar to those of WKY rats. Furthermore, we investigated the role of MR in the hypertensive rats by i.c.v. injection of the MR antagonist RU-2831. This compound produced a significant drop in blood pressure for SHR. In conclusion, MR expression is increased in the hippocampus and hypothalamus of SHR. We suggest that pathological MR overdrive may take responsibility for up-regulation of blood pressure and the encephalopathy of hypertension.

Changes of hypothalamic and plasma vasopressin in rats with deoxycorticosterone-acetate induced salt appetite.

Mineralocorticoids play a predominant role in development of salt appetite and hypertension. Since vasoactive peptides could mediate the central effects of mineralocorticoids, we evaluated changes of immunoreactive (IR) arginine vasopressin (AVP) in the paraventricular (PVN) and supraoptic (SON) hypothalamic nucleus during DOCA-induced salt appetite. In one model, rats having free access to water and 3% NaCl during 9 (prehypertensive stage) or 21 days (hypertensive stage) received DOCA (s.c., 10 mg/rat/in alternate days). A decrease in the IR cell area, number of IR cells and staining intensity was obtained in magnocellular PVN of rats treated during 9 days. After 21 days IR cell area and number of cells in the PVN also decreased, but staining intensity of remaining cells was normal. The same parameters were unchanged in the SON. In another model, animals treated with DOCA during 9 days had only access to 3% NaCl or water. The IR cell area in PVN and SON significantly increased in mineralocorticoid-treated and control animals, both drinking 3% NaCl. Staining intensity (PVN and SON) and number of IR cells (PVN) also augmented in DOCA-treated animals drinking salt respect of a group drinking water. Plasma AVP in rats treated with DOCA and offered salt and water, exhibited a 2-2.5 fold increase at the time of salt appetite induction. Plasma AVP was substantially higher in rats drinking salt only, while the highest levels were present in salt-drinking DOCA-treated rats. Thus, peptide depletion in the PVN may be due to increased release, because reduced levels of hypothalamic and posterior pituitary AVP were measured in this model. In rats drinking salt only the substantial increase of IR AVP in the PVN and SON, may be due to dehydration and hyperosmosis. Because DOCA-salt treated rats showed higher AVP levels in the PVN compared to untreated rats drinking salt only, it is possible that DOCA sensitized PVN cells to increase AVP production. The results suggest the vasopressinergic system could mediate some central functions of mineralocorticoids.