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

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 the present study, we 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. Accordingly, in the hippocampus, we measured mRNA expression and immunoreactivity of the MR and glucocorticoid receptor ( GR ) using a quantitative polymerase chain reaction and histochemistry. We also measured serum‐glucocorticoid‐activated kinase 1 ( Sgk1 mRNA ), the number and phenotype of Iba1+ microglia, as well as mRNA expression levels of the pro‐inflammatory factors cyclo‐oxygenase 2 ( Cox2 ), Nlrp3 inflammasome and tumour necrosis factor α ( Tnf α). Expression of anti‐inflammatory transforming growth factor ( Tgf )β mRNA and the NADPH ‐diaphorase activity of nitric oxide synthase ( NOS ) were also determined. The results showed that, in the hippocampus of SHR rats, expression of MR and the number of immunoreactive MR / GR co‐expressing cells were increased compared to Wistar‐Kyoto control animals. Expression of Sgk1 , Cox2 , Nlrp3 and the number of ramified glia cells positive for Iba1+ were also increased, whereas Tgf β mRNA expression and the NADPH ‐diaphorase activity of NOS were decreased. We propose that, in the SHR hippocampus, increased MR expression causes a bias towards a pro‐inflammatory phenotype characteristic for hypertensive encephalopathy.