Estradiol Decreases MAPKs phosphorylation in Response to Angiotensin II by Increasing MKP‐1 in the Hypothalamus, but not in the Lamina Terminalis

Abstract

IntroductionThe angiotensin II (ANGII) plays an important role in the control of body fluids and estradiol (E2) modulates several actions of ANGII in the brain. Recently, our group showed that ERK1/2, JNK and p38MAPK are involved in sodium intake induced by ANGII in female rats. On the other hand, ANGII‐induced water intake requires JNK and p38MAPK, but not ERK1/2. In regarding to neurohypohysial hormone release, our group showed that ERK1/2 is involved in vasopressin (AVP) release but not in oxytocin (OT) release induced by ANGII. While ANGII‐induced OT release requires p38MAPK signaling. Therefore, herein the aim of study was evaluated whether E2 modulates MAPKs phosphorylation in response to ANGII as well MAPK phosphatase 1 (MKP‐1) which is responsible for inhibiting all the MAPKs (ERK1/2, JNK and p38MAPK) in the paraventricular (PVN) and supraoptic nuclei (SON) of hypothalamus, and in structures of lamina terminalis.Materials and MethodsWistar rats (~250g) were submitted to ovariectomy (OVX) and on the following day they were treated with estradiol cypionate (10μg/rat, sc, OVX+E2) or vehicle (corn oil, 0.1mL/rat, sc) for eight days. On the eighth day, the rats received an icv (lateral ventricle) injection of ANGII (25ng/2μL/rat) or vehicle (0.9% saline, 2μL/rat). After ten min of ANGII injection the animals were decapitated for brain collection for ERK1/2, JNK and p38MAPK total and phosphorylated, MKP‐1 and β‐Actin analyses by western blot. Data were analyzed using ANOVA two‐way, followed by Newman‐Keuls post‐test and the level of significance was set at 5%.ResultsThe treatment with E2 attenuated JNK and p38MAPK phosphorylation in response to ANGII in the lamina terminalis (E2 x ANGII interaction: F1,17=19.00, p<0.001; E2 x ANGII interaction: F1,29=6.1, p<0.05, respectively). In regarding to PVN and SON, it was observed that E2 attenuated ERK1/2 and p38MAPK phosphorylation in response to ANGII (E2 x ANGII interaction: F1,29=7.91, p<0.01; F1,26=4.1, p<0.05, respectively). E2, but not ANGII alone, was able to increase MKP‐1 expression in the PVN and SON (E2: F1,18=24.29, p<0.001), but not in the lamina terminalis.ConclusionThese results suggest that E2 dephosphorylates ERK1/2 and p38MAPK in response to ANGII by increasing MKP‐1 in the PVN and SON, but not in structures of lamina terminalis, such as subfornical organ, median preoptic nucleus and organum vasculosum of the lamina terminalis. E2 is able to dephosphorylate JNK and p38MAPK in the lamina terminalis in response to ANGII, however this effect does not involve MKP‐1.Support or Funding InformationFinancial support: FAPESP, CNPq and CAPES.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.