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

Abstract：

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 (1nmol/L to 10mmol/L) before and after incubation with Wortmannin (10nmol/L, 30min). 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 (10nmol/L) on the cytosolic concentrations of nitric oxide (NO; measured using 4,5-diaminofluorescein diacetate [DAF-2DA], 10mmol/L), Ca(2+) (using Fluo 3-AM, 5μmol/L) and reactive oxygen species (ROS; using dihydroethidium [DHE], 2.5mmol/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.

journal_name

Life Sci

journal_title

Life sciences

authors

Zancheta D,Troiano JA,Potje SR,Cavalari P,Sumida DH,Antoniali C

doi

10.1016/j.lfs.2014.12.014

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

78-86

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(14)00977-1

journal_volume

122

pub_type

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