Increased expression of the mineralocorticoid receptor in the brain of spontaneously hypertensive rat (SHR)

PIETRANERA, LUCIANA; ROIG, PAULINA; LIMA, ANALÍA; DE NICOLA, ALEJANDRO F.

Seefeld

Simposio; First International Symposium of The Journal: Hormone Molecular Biology and Clinical Investigation; 2010

Journal Hormone Molecular Biology and Clinical Investigation

Hippocampal neuropathology is a recognized feature of the spontaneously hypertensive rat (SHR). In previous studies we found that SHR present abnormalities in the hippocampus consisting of decreased cell proliferation in the dentate gyrus (DG), astroglial reactivity and decreased neuronal density in the hilus of the DG. Furthermore, hypertensive rats present a hyperfunction of the hypothalamus, i.e increased expression of the vasoactive neuropeptide arginine vasopressin (AVP) in the paraventricular nucleus (PVN) and hyperresponse to mineralocorticoid treatment. These abnormalities are reversed by exogenous administration of estradiol, an active neuroprotective agent. Also, we studied the endogenous biosyntesis of estradiol by measuring the expression of aromatase, the enzyme responsible for the syntesis of estradiol. We found aromatase expression increased in the hippocampus of SHR versus the normotensive strain WKY both at the mRNA and protein level. Mineralocorticoid effects in the brain include the control of cardiovascular functions, induction of salt appetite, interaction with AVP and angiotensin II and development or aggravation of hypertension. In this regard, mineralocorticoids may play a pathogenic role in SHR. We studied the expression of the mineralocorticoid receptor (MR) in the hippocampus and hypothalamus of 16 weeks old SHR and their normotensive controls WKY rats. MR mRNA expression was determined by Real Time PCR and in situ hybridization using riboprobes in the hippocampus. Hypertensive animals showed increased expression of MR mRNA in the hippocampus (p<0.05) both by real time PCR and in situ hybridization. In the hypothalamus, expression of the MR protein was determined by inmunohistochemistry. The inmunoreactive area and the intensity of the reaction were increased in the PVN of SHR compared to WKY (p<0.05 inmunoreactive area SHR vs WKY and p<0.01 iligv/area SHR vs. WKY). In conclusion, MR expression is upregulated in the hippocampus and hypothalamus of SHR. The increased MR expression may underlie the hyperresponse to mineralocorticoids and be involved in the encephalopathy of hypertension.