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Participation of pathway PI3-K/AKT/NOSe, glycosylation (O-GlcNAc) and EROs in hiporeatividade vascular and hypotension observed at the end of pregnancy in rats normotensive and SHR

Grant number: 12/20398-6
Support type:Regular Research Grants
Duration: February 01, 2013 - July 31, 2015
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Cristina Antoniali Silva
Grantee:Cristina Antoniali Silva
Home Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

Hypertensive disorders are the leading causes of maternal death worldwide. Thus it becomes essential to develop research to better understand this condition. Research has shown that in pregnant rats normotensive or hypertensive (SHR) there is a significant decrease in blood pressure in the final period of pregnancy directly associated with reduced sympathetic activity of perivascular mesenteric beds of normotensive or hypertensive rats (SHR). Furthermore, in situ or mesenteric beds isolated from normotensive or hypertensive rats (SHR) at the end of pregnancy also have decreased pressor responses to stimulation by front vasoconstrictor agents such as phenylephrine, vasopressin, serotonin and endothelin. These changes have been attributed to an important role of endothelium-derived relaxing factors (EDFRs) with emphasis on nitric oxide (NO). However, some studies showed that NO synthesis could not be due solely by calcium and recently dependence of NO production has been described also by phosphorylation of eNOS. The phosphorylation of eNOS activity depends on the route PI3-K/Akt/NOSe and that increased glicosaminação (O-GlcNAc) is involved in the reduction of phosphorylation of eNOS. In addition to increased NO production, pathways involved in increased NO bioavailability could also contribute to lower peripheral vascular resistance associated with pregnancy / gestation. Possible increases in the degradation of reactive oxygen species (ROS) during pregnancy could help reduce BP in pregnancy and modulation of vascular reactivity to vasoconstrictor agonists. This study aims to evaluate the role of phosphorylation of eNOS via PI3K-Akt and participation glicosaminação (O-GlcNAc) in modulating vascular reactivity observed in normotensive and hypertensive pregnant rats (SHR) in late pregnancy and the role of reactive species oxygen (ROS) in this modulation and evaluate the role of antioxidants in modulating the Mean Arterial Pressure (MAP) and Heart Rate (HR) about hypotension observed in normotensive and hypertensive pregnant rats (SHR) in late pregnancy. To achieve these objectives will be achieved in vivo experiments to evaluate the effect of antioxidants (APOCYNIN, TEMPOL) and eNOS inhibitor (L-NAME) on the baseline parameters of HR and MAP and also the pressor responses stimulated by Phe, ACh, and SNP . Vitro to assess the effect of wortmannin, PUGNAc, apocynin, NAC and PEGSOD vascular reactivity to Phe, Ach and SPL and also evaluation of cytosolic levels of NO, ROS and Ca+2 endothelial cells from aortas and biomolecular assays (Western Blott) to evaluate the expression of proteins involved in pathways of phosphorylation / dephosphorylation of eNOS and pathways involved in the bioavailability of NO. (AU)

Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
POTJE, SIMONE R.; TROIANO, JESSICA A.; GRANDO, MARCELLA D.; GRATON, MURILO E.; DA SILVA, ROBERTO S.; BENDHACK, LUSIANE M.; ANTONIALI, CRISTINA. Endothelial modulation of a nitric oxide donor complex-induced relaxation in normotensive and spontaneously hypertensive rats. Life Sciences, v. 201, p. 130-140, MAY 15 2018. Web of Science Citations: 0.
POTJE, SIMONE R.; TROIANO, JESSICA A.; GRATON, MURILO E.; XIMENES, VALDECIR F.; NAKAMUNE, ANA CLAUDIA M. S.; ANTONIALI, CRISTINA. Hypotensive and vasorelaxant effect of Diapocynin in normotensive rats. Free Radical Biology and Medicine, v. 106, p. 148-157, MAY 2017. Web of Science Citations: 7.
FALQUETTO, BARBARA; TUPPY, MARINA; POTJE, SIMONE R.; MOREIRA, THIAGO S.; ANTONIALI, CRISTINA; TAKAKURA, ANA C. Cardiovascular dysfunction associated with neurodegeneration in an experimental model of Parkinson's disease. Brain Research, v. 1657, p. 156-166, FEB 15 2017. Web of Science Citations: 10.
TROIANO, J. A.; POTJE, S. R.; GRATON, M. E.; CAVALARI, P.; PEREIRA, A. A. F.; VALE, G. T.; NAKAMUNE, A. C. M. S.; SUMIDA, D. H.; TIRAPELLI, C. R.; ANTONIALI, C. Decreased reactive oxygen species production and NOX1, NOX2, NOX4 expressions contribute to hyporeactivity to phenylephrine in aortas of pregnant SHR. Life Sciences, v. 144, p. 178-184, JAN 1 2016. Web of Science Citations: 5.
ZANCHETA, DALISE; TROIANO, JESSICA A.; POTJE, SIMONE R.; CAVALARI, PRISCILA; SUMIDA, DORIS H.; ANTONIALI, CRISTINA. The PI3K-Akt-eNOS pathway is involved in aortic hyporeactivity to Phenylephrine associated with late pregnancy in spontaneously hypertensive rats. Life Sciences, v. 122, p. 78-86, FEB 1 2015. Web of Science Citations: 4.

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