The PI3K-Akt-eNOS pathway is involved in aortic hyporeactivity to Phenylephrine associated with late pregnancy in spontaneously hypertensive rats

Autor(es)

Zancheta, Dalise ^{[1, 2]} ; Troiano, Jessica A. ^{[1, 2]} ; Potje, Simone R. ^{[1, 2]} ; Cavalari, Priscila ^{[2, 3]} ; Sumida, Doris H. ^{[1, 2]} ; Antoniali, Cristina ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] SBFis, Programa Posgrad Multicent Ciencias Fisiol, Rio De Janeiro - Brazil

^[2] UNESP, Sch Dent Aracatuba, Dept Basic Sci, BR-16015050 Aracatuba, SP - Brazil

^[3] Univ Paulista, Sch Pharm Aracutuba, Aracatuba, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 122, p. 78-86, FEB 1 2015.
• Citações Web of Science: 4

Resumo

Aim: This study aimed to evaluate the effects of Wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), on aortic hyporeactivity to Phenylephrine (Phe) and nitric oxide bioavailability associated with pregnancy in hypertensive rats. Main methods: The intact aortic rings of pregnant and non-pregnant Wistar or spontaneously hypertensive rats (SHRs) were stimulated with Phe (1 nmol/L to 10 mmol/L) before and after incubation with Wortmannin (10 nmol/L, 30 min). Western blot experiments analyzed the expression of phosphorylated PI3K {[}p85-PI3K], Akt {[}p-Akt (Ser 473)] and eNOS {[}p-eNOS (Ser 1177)] in aorta homogenates of pregnant and non-pregnant Wistar rats or SHRs. The effect of Wortmannin (10 nmol/L) on the cytosolic concentrations of nitric oxide (NO; measured using 4,5-diaminofluorescein diacetate {[}DAF-2DA], 10 mmol/L), Ca2+ (using Fluo 3-AM, 5 mu mol/L) and reactive oxygen species (ROS; using dihydroethidium {[}DHE], 2.5 mmol/L) were measured fluorimetrically in freshly isolated endothelial cells. Key findings: Wortmannin increases the reactivity of the aorta to Phe and decreases NO concentrations in the aortic endothelial cells of pregnant Wistar rats and SHR. Significance: The PI3/AKT/endothelial nitric oxide synthase (eNOS) pathway contributes to aortic hyporeactivity to Phenylephrine associated with pregnancy in normo- and hypertensive rats. (C) 2014 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 12/20398-6 - Participação da via PI3-K/Akt/NOSe, glicosaminação (O-GlcNAc) e EROs na hiporeatividade vascular e hipotensão observada ao final da prenhez de ratas normotensas e espontaneamente hipertensas (SHR)
• Beneficiário: Cristina Antoniali Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/05746-8 - Estudo da participação da eNOS fosforilada em resíduos de serina 1177 e treonina 495 na hiporeatividade da aorta à fenilefrina observada ao final da prenhez em ratas normotensas e espontaneamente hipertensas (SHR)
• Beneficiário: Dalise Zancheta
• Modalidade de apoio: Bolsas no Brasil - Mestrado