title: Increased expression of the mineralocorticoid receptor in the brain of spontaneously hypertensive rats.
abstract: 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.
authors.affiliation: Institute of Biology and Experimental Medicine, CONICET, Obligado, Buenos Aires, Argentina.
authors.forename: L
authors.initials: L
authors.lastname: Pietranera
authors.forename: M E
authors.initials: ME
authors.lastname: Brocca
authors.forename: C
authors.initials: C
authors.lastname: Cymeryng
authors.forename: E
authors.initials: E
authors.lastname: Gomez-Sanchez
authors.forename: C E
authors.initials: CE
authors.lastname: Gomez-Sanchez
authors.forename: P
authors.initials: P
authors.lastname: Roig
authors.forename: A
authors.initials: A
authors.lastname: Lima
authors.forename: A F
authors.initials: AF
authors.lastname: De Nicola
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011921:Rats, Inbred WKY; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis; D018161:Receptors, Mineralocorticoid / Q000096:biosynthesis*; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; C041006:RU 28318