title: Decreased reactive oxygen species production and NOX1, NOX2, NOX4 expressions contribute to hyporeactivity to phenylephrine in aortas of pregnant SHR.
abstract: OBJECTIVE
  We determined whether decreased reactive oxygen species (ROS) production in the aorta of pregnant spontaneously hypertensive rats (SHR) resulted in increased nitric oxide (NO) bioavailability and hyporeactivity to phenylephrine (PE).
  
  
  METHODS
  Systemic and aortic oxidative stress were measured in pregnant and non-pregnant Wistar rats and SHR. Furthermore, the hypotensive effects of apocynin (30 mg/kg) and Tempol (30 mg/kg) were analyzed. Intact aortic rings of pregnant and non-pregnant rats were stimulated with PE in the absence of or after incubation (30 min) with apocynin (100 μmol/L). The effect of apocynin on the concentrations of NO and ROS were measured in aortic endothelial cells (AEC) using DAF-2DA (10 mmol/L) and DHE (2.5 mmol/L), respectively. Western blotting was performed to analyze eNOS, NOX1, NOX2, NOX4 and SOD expression. ROS production was analyzed by the lucigenin chemiluminescence method.
  
  
  RESULTS
  Aortic oxidative stress and ROS concentration in AEC were reduced in pregnant Wistar rats and SHR, when compared to non-pregnant rats. ROS production and NOX1, NOX2 and NOX4 expression in the aortas were decreased in pregnant SHR, but not in pregnant Wistar rats. Increased eNOS expression in aortas and NO concentration in AEC were observed in pregnant Wistar rats and SHR. Apocynin reduced PE-induced vasoconstriction in the aortas of non-pregnant Wistar rats and SHR, and pregnant Wistar rats, but not in the aortas of pregnant SHR.
  
  
  CONCLUSIONS
  Taken together, these results suggest that ROS production was decreased in the aortas of pregnant SHR and could contribute to higher NO bioavailability and hyporeactivity to PE in the aortas of pregnant SHR.
authors.affiliation: Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, SBFis, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, São Paulo, Brazil.
authors.forename: J A
authors.initials: JA
authors.lastname: Troiano
authors.affiliation: Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, SBFis, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, São Paulo, Brazil.
authors.forename: S R
authors.initials: SR
authors.lastname: Potje
authors.affiliation: Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, SBFis, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, São Paulo, Brazil.
authors.forename: M E
authors.initials: ME
authors.lastname: Graton
authors.affiliation: Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, São Paulo, Brazil; School of Pharmacy of Araçatuba, UNIP - Univ Paulista, Araçatuba, São Paulo, Brazil.
authors.forename: P
authors.initials: P
authors.lastname: Cavalari
authors.affiliation: Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, SBFis, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, São Paulo, Brazil.
authors.forename: A A F
authors.initials: AA
authors.lastname: Pereira
authors.affiliation: Department of Psychiatry Nursing and Human Sciences, College of Nursing of Ribeirão Preto, USP - University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: G T
authors.initials: GT
authors.lastname: Vale
authors.affiliation: Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, SBFis, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, São Paulo, Brazil.
authors.forename: A C M S
authors.initials: AC
authors.lastname: Nakamune
authors.affiliation: Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, SBFis, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, São Paulo, Brazil.
authors.forename: D H
authors.initials: DH
authors.lastname: Sumida
authors.affiliation: Department of Psychiatry Nursing and Human Sciences, College of Nursing of Ribeirão Preto, USP - University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: C R
authors.initials: CR
authors.lastname: Tirapelli
authors.affiliation: Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, SBFis, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, São Paulo, Brazil. Electronic address: crisant@foa.unesp.br.
authors.forename: C
authors.initials: C
authors.lastname: Antoniali
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology*; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009247:NADH, NADPH Oxidoreductases / Q000096:biosynthesis*; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000096:biosynthesis*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D010656:Phenylephrine; D009569:Nitric Oxide; D009247:NADH, NADPH Oxidoreductases; C500593:Cybb protein, rat; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C000614712:NOX1 protein, rat; C498911:Nox4 protein, rat
keywords: Aorta; Hypertension; Hyporeactivity; Pregnancy; Reactive oxygen species