title: Apocynin reduces blood pressure and restores the proper function of vascular endothelium in SHR.
abstract: This study has evaluated how the vascular endothelium of hypertensive rats chronically treated with apocynin affects acetylcholine (ACh), sodium nitroprusside (SNP), and phenylephrine (PE) action on the nitric oxide (NO) signal transduction pathway in endothelial (EC) and vascular smooth muscle cells. Treatment with apocynin significantly reduced the mean arterial pressure in spontaneously hypertensive rats (SHR). In addition, apocynin improved the impaired ACh hypotensive effect on SHR. Although systemic oxidative stress was high in SHR, SHR treated with apocynin and normotensive rats presented similar systemic oxidative stress levels. Endothelium significantly blunted PE contractions in intact aortas of treated SHR. The ACh effect was impaired in resistance arteries and aortas of SHR, but this same effect was improved in treated SHR. The SNP potency was higher in intact resistance arteries of treated SHR than in intact resistance arteries of untreated SHR. NO and calcium concentrations increased, whereas reactive oxygen species levels decreased in EC of treated SHR. Aortas of untreated and treated SHR did not differ in terms of sGC alpha or beta units expression. Aorta of treated SHR expressed higher eNOS levels as compared to aorta of untreated SHR. The study groups did not differ with respect to NOX1, NOXO1, or NOX4 expression. However, treatment with apocynin normalized overexpression of NOX2 and its subunit p47phox in aortas of SHR. Based on all the results presented in this study, we suggest apocynin increases NO biovailability by different mechanisms, restoring the proper function of vascular endothelium in SHR.
authors.affiliation: Multicenter Graduate Program in Physiological Sciences, SBFis, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, São Paulo, Brazil.
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Perassa
authors.affiliation: Multicenter Graduate Program in Physiological Sciences, SBFis, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, São Paulo, Brazil.
authors.forename: Murilo E
authors.initials: ME
authors.lastname: Graton
authors.affiliation: Multicenter Graduate Program in Physiological Sciences, SBFis, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, São Paulo, Brazil.
authors.forename: Simone R
authors.initials: SR
authors.lastname: Potje
authors.affiliation: Multicenter Graduate Program in Physiological Sciences, SBFis, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, São Paulo, Brazil.
authors.forename: Jéssica A
authors.initials: JA
authors.lastname: Troiano
authors.affiliation: Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, São Paulo, Brazil.
authors.forename: Mariana S
authors.initials: MS
authors.lastname: Lima
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: Gabriel T
authors.initials: GT
authors.lastname: Vale
authors.affiliation: Multicenter Graduate Program in Physiological Sciences, SBFis, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, São Paulo, Brazil.
authors.forename: Ariana A F
authors.initials: AA
authors.lastname: Pereira
authors.affiliation: Multicenter Graduate Program in Physiological Sciences, SBFis, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, São Paulo, Brazil.
authors.forename: Ana Claúdia M S
authors.initials: AC
authors.lastname: Nakamune
authors.affiliation: Multicenter Graduate Program in Physiological Sciences, SBFis, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, São Paulo, Brazil.
authors.forename: Doris 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: Carlos R
authors.initials: CR
authors.lastname: Tirapelli
authors.affiliation: Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, USP - University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Lusiane M
authors.initials: LM
authors.lastname: Bendhack
authors.affiliation: Multicenter Graduate Program in Physiological Sciences, 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: Cristina
authors.initials: C
authors.lastname: Antoniali
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000098:Acetophenones; D017382:Reactive Oxygen Species; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; C056165:acetovanillone; D000109:Acetylcholine; D002118:Calcium
keywords: Apocynin; Endothelial dysfunction; Reactive oxygen species; SHR; eNOS