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Study of post-translational modification mechanisms that increase the bioavailability of nitric oxide in blood vessels of normotensive and spontaneously hypertensive rats SHR at the end of pregnancy.

Grant number: 16/22180-9
Support Opportunities:Regular Research Grants
Duration: June 01, 2017 - November 30, 2019
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Principal Investigator:Cristina Antoniali Silva
Grantee:Cristina Antoniali Silva
Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
Associated researchers:Simone Regina Potje

Abstract

Previous studies from our laboratory suggest that pregnancy is a favorable physiological condition to reduced blood pressure, vascular reactivity to ±1-adrenergic stimulation and to reestablishment of the endothelial function in spontaneously hypertensive rats (SHR). In pregnant SHR, the increased production and bioavailability of NO, resulting from increased phosphorylation of the PI3K-Akt- eNOS pathway, reestablished endothelium-eNOS-dependent modulation on aortas reactivity to phenylephrine (PE). The objective of this study is to analyze possible alterations in post-translational modification mechanisms associated to increased eNOS activity in blood vessel of pregnant SHR. The glycosylation of eNOS by hexosamine pathway and protein-protein interactions associated to eNOS phosphorylation will be investigate in blood vessel of normotensive pregnant rats and pregnant SHR. Western Blot Assays will performed to analyze following proteins expression: NOXO1, p47phox, O-GlcNAc transferase, O-GlcNAc, eNOS, p-eNOS, CAV-1, P-CAV-1, Hsp90, p-Hsp90, calmodulin (CaM), Src, p-Src and anti-NQO1 and Nrf2 as well as their interactions by co-immunoprecipitation method. In functional studies, we will evaluate the participation of pos-translational mechanisms on vascular hiporeactivity to phenilefrine associated to pregnancy. We will evaluate the participation of OGA, by inhibition with PUGNAc (100 mmol / L), Hsp90 by inhibition with Geldamycin (1 mmol / L) or radicicol (20 nmol / L), and Src by inhibition with PP2 drug (15 mmol / L). The intracellular concentrations of NO and hydrogen peroxide (H2O2) in endothelial cell of pregnant rats will be analyzed by flow cytometry. The results will be analyzed by ANOVA multivariance test, two-way, and the significative differences will be considered when p <0.05. (AU)

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Scientific publications (12)
(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)
NATALI, LUIZ HENRIQUE; TROIANO, JESSICA ANTONINI; POTJE, SIMONE REGINA; MARTINS DIAS, DANIEL PENTEADO; ANTONIALI, CRISTINA. Pregnancy restores altered sympathetic vasomotor modulation and parasympathetic cardiac modulation in hypertensive rats. PREGNANCY HYPERTENSION-AN INTERNATIONAL JOURNAL OF WOMENS CARDIOVASCULAR HEALTH, v. 28, p. 9-pg., . (16/22180-9, 12/20398-6)
GRATON, MURILO E.; FERREIRA, BRUNO H. S. H.; TROIANO, JESSICA A.; POTJE, SIMONE. R. R.; VALE, GABRIEL. T. T.; NAKAMUNE, ANA CLAUDIA M. S.; TIRAPELLI, CARLOS R.; MILLER, FRANCIS. J. J.; XIMENES, VALDECIR. F. F.; ANTONIALI, CRISTINA. Comparative study between apocynin and protocatechuic acid regarding antioxidant capacity and vascular effects. FRONTIERS IN PHYSIOLOGY, v. 13, p. 14-pg., . (16/22180-9, 16/01476-7, 17/18436-0, 14/50926-0)
GRATON, MURILO E.; POTJE, SIMONE R.; TROIANO, JESSICA A.; VALE, GABRIEL T.; PERASSA, LIGIA A.; NAKAMUNE, ANA CLAUDIA M. S.; TIRAPELLI, CARLOS R.; BENDHACK, LUSIANE M.; ANTONIALI, CRISTINA. Apocynin alters redox signaling in conductance and resistance vessels of spontaneously hypertensive rats. Free Radical Biology and Medicine, v. 134, p. 53-63, . (16/22180-9)
ARAUJO, HEITOR CEOLIN; NAKAMUNE, ANA CLAUDIA MELO STEVANATO; GARCIA, WILSON GALHEGO; PESSAN, JULIANO PELIM; ANTONIALI, CRISTINA. Carious Lesion Severity Induces Higher Antioxidant System Activity and Consequently Reduces Oxidative Damage in Children's Saliva. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, v. 2020, . (16/22180-9)
POTJE, SIMONE R.; GRANDO, MARCELLA D.; CHIGNALIA, ANDREIA Z.; ANTONIALI, CRISTINA; BENDHACK, LUSIANE M.. Reduced caveolae density in arteries of SHR contributes to endothelial dysfunction and ROS production. SCIENTIFIC REPORTS, v. 9, . (17/14797-9, 16/22180-9, 16/21239-0)
TROIANO, JESSICA A.; POTJE, SIMONE R.; GRATON, MURILO E.; SILVA, DANIELA S.; DA COSTA, RAFAEL M.; TOSTES, RITA C.; ANTONIALI, CRISTINA. Pregnancy decreases O-GlcNAc-modified proteins in systemic arteries of normotensive and spontaneously hypertensive rats. Life Sciences, v. 266, . (16/22180-9, 15/09373-0)
GRATON, MURILO; BENEVIDES, PRISCILA SCARPIM; TROIANO, JESSICA ANTONINI; POTJE, SIMONE REGINA; GONCALVES, EMILY; ZANARDO, JESSICA; NAKAMUNE, ANA CLAUDIA; ANTONIALI, CRISTINA. Antioxidant Defense in Mesenteric Arteries from Spontaneously Hypertensive Rats Treated with Apocynin. Free Radical Biology and Medicine, v. 145, p. 1-pg., . (19/13751-0, 16/22180-9, 17/18436-0)
GRATON, MURILO EDUARDO; POTJE, SIMONE REGINA; TROIANO, JESSICA ANTONINI; DO VALE, GABRIEL TAVARES; BENEVIDES, PRISCILA SCARPIM; GONCALVES, EMILY THALIA; NAKAMUNE, ANA CLAUDIA DE MELO STEVANATO; TIRAPELLI, CARLOS RENATO; BENDHACK, LUSIANE MARIA; ANTONIALI, CRISTINA. Apocynin Alters Redox Signaling in Blood Vessels of Spontaneously Hypertensive Rats. FASEB JOURNAL, v. 33, p. 2-pg., . (16/22180-9)
TROIANO, JESSICA ANTONINI; GRATON, MURILO EDUARDO; POTJE, SIMONE REGINA; GONCALVES, EMILY THALIA; DE OLIVEIRA FONSECA ZANARDO, JESSICA LUIZA; BENEVIDES, PRISCILA SCARPIM; ANTONIALI, CRISTINA. Distinct Role of Endothelial Caveolae in Contraction and Relaxation Responses of Aortas from Pregnant Normotensive and hypertensive Rates. FASEB JOURNAL, v. 33, p. 2-pg., . (18/10635-7, 15/09373-0, 16/22180-9)
BARROSO, HELENA C.; GRATON, MURILO E.; POTJE, SIMONE R.; TROIANO, JESSICA A.; SILVA, LILIAN X.; NAKAMUNE, ANA CLAUDIA M. S.; ANTONIALI, CRISTINA. Data of Nebivolol on oxidative stress parameters in hypertensive patients. DATA IN BRIEF, v. 41, p. 11-pg., . (16/22180-9, 17/18436-0, 15/09373-0)
TROIANO, JESSICA ANTONINI; POTJE, SIMONE REGINA; GRATON, MURILO; SILVA, DANIELA DE SOUZA; COSTA, RAFAEL MENEZES; TOSTES, RITA DE CASSIA; ANTONIALI, CRISTINA. O-GlcNAcylation is decreased in aorta and mesenteric artery in normotensive and hypertensive pregnant rats. Free Radical Biology and Medicine, v. 128, p. 1-pg., . (16/22180-9, 15/09373-0)
GRATON, MURILO; POTJE, SIMONE REGINA; TROIANO, JESSICA ANTONINI; VALE, GABRIEL TAVARES; BENEVIDES, PRISCILA SCARPIM; TIRAPELLI, CARLOS RENATO; NAKAMUNE, ANA CLAUDIA; BENDHACK, LUSIANE MARIA; ANTONIALI, CRISTINA. Apocynin reduces pressor and vasoconstrictor effects of Ang II in SHR. Free Radical Biology and Medicine, v. 128, p. 1-pg., . (16/22180-9)

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