Efeito da apocinina na hipertensão, disfunção endotelial e hipertrofia ventricular esquerda em Ratos Espontaneamente Hipertensos (SHR)
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Data
2013-07-31
Autores
Perassa, Lígia Arnedo [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
As enzimas NAD(P)H oxidases ou família NOX tem sido considerada a principal fonte de espécies reativas de oxigênio (ERO) em vários tipos celulares. O aumento da biodisponibilidade de ERO e do sinal redox (estresse oxidativo) têm sido associados ao início e ou progressão de doenças crônicas como a hipertensão. Inibidores da NAD(P)H oxidase, como a apocinina, foram desenvolvidos e seus efeitos anti-hipertensivos têm sido estudados. O objetivo deste estudo foi verificar se o tratamento crônico com apocinina previne o desenvolvimento da hipertensão, da disfunção endotelial e da hipertrofia ventricular esquerda em Ratos Espontaneamente Hipertensos (SHR) e avaliar os possíveis mecanismos envolvidos nestes efeitos. Para isto, ratos normotensos Wistar e SHR foram tratados com apocinina (30 mg/kg/dia, diluída na água de beber) da quarta até a décima semana de vida. Foram realizados experimentos in vivo para avaliação de valores basais de pressão arterial (média - PAM, sistólica - PS e diastólica - PD), freqüência cardíaca (FC) e as respostas às drogas hipotensoras, acetilcolina (ACh) e nitroprussiato de sódio (NPS) e pressoras, fenilefrina (Phe) e angiotensina II (ANGII). Experimentos in vitro foram realizados para determinar se o tratamento com apocinina promove alterações na concentração citosólica de cálcio intracelular ([Ca2+]), de óxido nítrico ([NO]) e de espécies reativas de oxigênio ([ERO]) nas células endoteliais (citometria de fluxo), estimuladas ou não com acetilcolina; na expressão proteica (Western Blotting) de enzima óxido nítrico sintase endotelial...
The enzymes NAD(P)H oxidases or family NOX has been considered the main source of reactive oxygen species (ROS) in various cell types. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in the onset and/or progression of chronic diseases, including hypertension. NAD(P)H oxidase inhibitors, such as apocynin were developed and their antihypertensive effects have been studied. The aim of this study was to determine whether chronic treatment with apocynin prevents the development of hypertension, endothelial dysfunction and left ventricular hypertrophy in spontaneously hypertensive rats (SHR) and to evaluate the mechanisms involved in these effects. Normotensive Wistar rats and SHR were treated with apocynin (30 mg/kg/day, diluted in the drinking water) from the fourth to the tenth week of life. The studies in vivo were performed to assess baseline blood pressure (mean arterial pressure - MAP, systolic - SBP, and diastolic blood pressure - DBP), heart rate (HR) before and after the administration of acetylcholine (ACh), sodium nitroprusside (SNP), phenylephrine (Phe) and angiotensin II (ANG II). We performed experiments in vitro to determine whether the treatment with apocynin causes changes in: cytosolic concentration of intracellular calcium ([Ca2+]), nitric oxide ([NO]), and reactive oxygen species ([ROS]) in endothelial cells (flow cytometry) stimulated or not with acetylcholine; protein expression (Western blotting) of enzyme endothelial nitric oxide synthase (eNOS) and of soluble guanylate cyclase...
The enzymes NAD(P)H oxidases or family NOX has been considered the main source of reactive oxygen species (ROS) in various cell types. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in the onset and/or progression of chronic diseases, including hypertension. NAD(P)H oxidase inhibitors, such as apocynin were developed and their antihypertensive effects have been studied. The aim of this study was to determine whether chronic treatment with apocynin prevents the development of hypertension, endothelial dysfunction and left ventricular hypertrophy in spontaneously hypertensive rats (SHR) and to evaluate the mechanisms involved in these effects. Normotensive Wistar rats and SHR were treated with apocynin (30 mg/kg/day, diluted in the drinking water) from the fourth to the tenth week of life. The studies in vivo were performed to assess baseline blood pressure (mean arterial pressure - MAP, systolic - SBP, and diastolic blood pressure - DBP), heart rate (HR) before and after the administration of acetylcholine (ACh), sodium nitroprusside (SNP), phenylephrine (Phe) and angiotensin II (ANG II). We performed experiments in vitro to determine whether the treatment with apocynin causes changes in: cytosolic concentration of intracellular calcium ([Ca2+]), nitric oxide ([NO]), and reactive oxygen species ([ROS]) in endothelial cells (flow cytometry) stimulated or not with acetylcholine; protein expression (Western blotting) of enzyme endothelial nitric oxide synthase (eNOS) and of soluble guanylate cyclase...
Descrição
Palavras-chave
NADPH Oxidase, Hipertensão, Vasodilatação, Endotelio, Hipertrofia ventricular esquerda, Ratos endogâmicos SHR
Como citar
PERASSA, Lígia Arnedo. Efeito da apocinina na hipertensão, disfunção endotelial e hipertrofia ventricular esquerda em Ratos Espontaneamente Hipertensos (SHR). 2013. 101 f. Dissertação (mestrado) - Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Odontologia de Araçatuba, 2013.