Increased Expression of the Mineralocorticoid Receptor in the Brain of Spontaneously Hypertensive Rats

• Published in: Journal of neuroendocrinology 2012-09, Vol.24 (9), p.1249-1258
• Main Authors: Pietranera, L., Brocca, M. E., Cymeryng, C., Gomez-Sanchez, E., Gomez-Sanchez, C. E., Roig, P., Lima, A., De Nicola, A. F.
• Format: Article
• Language: English
• Subjects: aldosterone; Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood pressure; Blood Pressure - drug effects; Brain; Cardiology. Vascular system; Central nervous system; cortisol/corticosterone; Data processing; Encephalopathy; Experimental diseases; Fundamental and applied biological sciences. Psychology; Gene expression; Glucocorticoid receptors; glucocorticoids; Hippocampus; Hippocampus - metabolism; Hypertension; Hypothalamus; Hypothalamus - metabolism; Immunohistochemistry; Medical sciences; membrane/nuclear; Mineralocorticoid Receptor Antagonists - pharmacology; Mineralocorticoid receptors; mineralocorticoids; mRNA; neuroactive steroids; Neuroprotection; Polymerase chain reaction; Rats; Rats, Inbred SHR - metabolism; Rats, Inbred WKY; receptors; Receptors, Glucocorticoid - biosynthesis; Receptors, Mineralocorticoid - biosynthesis; Spironolactone - analogs & derivatives; Spironolactone - pharmacology; steroids; Vertebrates: endocrinology
• ISSN: 0953-8194; 1365-2826
• DOI: 10.1111/j.1365-2826.2012.02332.x

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.