EFFECTS OF SELECTIVE ESTROGEN RECEPTOR AGONISTS ON ALTERED HYPOTHALAMIC PARAMETERS OF SPONTANEOUSLY HYPERTENSIVE RATS

BROCCA, M. ELVIRA; DE NICOLA, ALEJANDRO F.; BROCCA, M. ELVIRA; DE NICOLA, ALEJANDRO F.; CORREA, JULIETA; ROIG, PAULINA; CORREA, JULIETA; ROIG, PAULINA; LABOMBARDA, FLORENCIA; PIETRANERA, LUCIANA; LABOMBARDA, FLORENCIA; PIETRANERA, LUCIANA

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Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2016

Hippocampal neuropathology is a recognized feature of the spontaneouslyhypertensive rat (SHR). Previous studies have found that SHR presentabnormalities in the hippocampus consisting of decreased cell proliferation inthe dentate gyrus (DG), astroglial reactivity and decreased neuronal density inthe hilus of the DG. Hypertensive rats also present a hyperfunction ofhypothalamic neuropeptides, as shown by increased expression of the vasoactive neuropeptide arginine vasopressin (AVP)in the paraventricular nucleus (PVN) and hyperresponse of AVP followingmineralocorticoid treatment. Additionally, the SHR shows increased expressionof the mineralocorticoid receptor (MR) both in the hippocampus and the PVN.These abnormalities are reversed by exogenous administration of estradiol, anactive neuroprotective and hypotensive factor. Two types of estradiol receptors(ER) are expressed in the hypothalamus. To elucidate which ER subtype isinvolved in the hypothalamic effects, we used agonists of the ERa (propylpyrazole triol ,PPT) and the ERb (diarylpropionitrite, DPN) given s.c. during 2 weeks at 2.5 mg/kg every otherday to 4 month old male SHR. We measured the expression of AVP mRNA in thehypothalamus using real time PCR. We found that hypertensive animals haveincreased expression of AVP mRNA in the hypothalamus (p<0.05). Treatmentwith both specific agonists PPT and DPN significantly reversed this increment(p<0.05). Pro-inflammatory cytokines, such as TNFa can also stimulate AVP inthe hypothalamus. Therefore, we measured TNFa mRNA in SHR and found inthis strain a slight, although not significant increase of TNFa expression.However, treatment with both PPT and DPN reduced TNFa mRNA expression in thehypothalamus of SHR (p<0.05).  These data indicate that both estradiol classical receptors are involvedin the reduction of AVP overexpression. These effects may be due to directeffects upon the AVP gene or by down-regulation of TNFa expression.