Mineralocorticoid receptor associates with pro-inflammatory bias in hippocampus of spontaneously hypertensive rats

Abstract

Damage observed in the hippocampus of the adult spontaneously hypertensive rat (SHR) resembles the neuropathology of mineralocorticoid-induced hypertension, supporting a similar endocrine dysfunction in both entities. In this study we have tested the hypothesis that increased expression of the hippocampal mineralocorticoid receptor (MR) in SHR animals is associated with a prevalent expression of pro-inflammatory over anti-inflammatory factors. For this purpose we measured in hippocampus mRNA expression and immunoreactivity of the MR and the glucocorticoid receptor (GR) using qPCR and histochemistry. We also measured the serum-glucocorticoid-activated kinase 1 (Sgk1 mRNA), the number and phenotype of Iba1+ microglia, mRNA expression levels of the proinflammatory factors cyclooxygenase 2 (Cox2), Nlrp3 inflammasome and tumor necrosis factor alpha (Tnfα). The expression of anti-inflammatory Tgfβ mRNA and the NADPH-diaphorase activity of nitric oxide synthase (NOS) was also determined. The results showed that in the hippocampus of SHR rats the expression of MR and the number of immunoreactive MR / GR co-expressing cells is increased as compared to the Wistar Kyoto control animals. The expression of Sgk1, Cox2, Nlrp3 and the number of ramified glia cells positive for Iba1+ is increased, while Tgfβ mRNA expression and the NADPH-diaphorase activity of NOS are decreased. We propose that in the SHR hippocampus increased MR expression causes a bias towards a pro-inflammatory phenotype characteristic for hypertensive encephalopathy.

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