Mineralocorticoid Receptors, Neuroinflammation and Hypertensive Encephalopathy.
Maria Elvira BroccaLuciana PietraneraEdo Ronald de KloetAlejandro Federico De NicolaPublished in: Cellular and molecular neurobiology (2018)
Worldwide, raised blood pressure is estimated to affect 35-40% of the adult population and is a main conditioning factor for cardiovascular diseases and stroke. Animal models of hypertension have provided great advances concerning the pathophysiology of 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 of the brain in chronic hypertension. This review summarises present and past evidence that in the SHR, hypertension causes hippocampal 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 than aldosterone. Increased MR expression is a generalised feature of the SHR which seems to support first the rise in blood pressure. Then oxidative stress caused by vasculopathy and hypoxia further increases MR activation in hippocampal neurons and 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 expression levels and blockage with an antagonist failed to reduce blood pressure of SHR. The findings support the concept that MR:GR imbalance caused by vasculopathy causes a switch in MR function towards a proverbial "death" receptor.
Keyphrases
- blood pressure
- oxidative stress
- contrast enhanced
- hypertensive patients
- magnetic resonance
- heart rate
- cerebral ischemia
- induced apoptosis
- poor prognosis
- endothelial cells
- cardiovascular disease
- magnetic resonance imaging
- binding protein
- resting state
- blood glucose
- ischemia reperfusion injury
- adipose tissue
- white matter
- dna damage
- machine learning
- metabolic syndrome
- spinal cord
- traumatic brain injury
- weight loss
- diabetic rats
- inflammatory response
- cell proliferation
- signaling pathway
- long non coding rna
- early onset
- angiotensin ii
- functional connectivity
- heat shock
- cell death
- cardiovascular events
- heat shock protein