Mineralocorticoid Receptors, Neuroinflammation and Hypertensive Encephalopathy

BROCCA, MARIA ELVIRA; PIETRANERA, LUCIANA; DE KLOET, EDO RONALD; DE NICOLA, ALEJANDRO FEDERICO

CELLULAR AND MOLECULAR NEUROBIOLOGY.

SPRINGER/PLENUM PUBLISHERS

Lugar: new york; Año: 2019 vol. 39 p. 483 - 492

0272-4340

Worldwide, raised blood pressure is estimated to affect 35?40% of the adult population and is a main conditioning factorfor cardiovascular diseases and stroke. Animal models of hypertension have provided great advances concerning the pathophysiologyof human hypertension, as already shown for the deoxycorticosterone-salt treated rat, the Dahl-salt sensitive rat,the Zucker obese rat and the spontaneously hypertensive rat (SHR). SHR has been widely used to study abnormalities ofthe brain in chronic hypertension. This review summarises present and past evidence that in the SHR, hypertension causeshippocampal tissue damage which triggers a pro-inflammatory feedforward cascade affecting this vulnerable brain region.The cascade is driven by mineralocorticoid receptor (MR) activation responding to endogenous corticosterone rather thanaldosterone. Increased MR expression is a generalised feature of the SHR which seems to support first the rise in bloodpressure. Then oxidative stress caused by vasculopathy and hypoxia further increases MR activation in hippocampal neuronsand glia cells, activates microglia activation and pro-inflammatory mediators, and down-regulates anti-inflammatory factors.In contrast to MR, involvement of the glucocorticoid receptor (GR) in SHR is less certain. GR showed normal expressionlevels and blockage with an antagonist failed to reduce blood pressure of SHR. The findings support the concept that MR:GRimbalance caused by vasculopathy causes a switch in MR function towards a proverbial ?death? receptor.