当前位置： SCI文献检索 > BRAIN RESEARCH期刊下所有文献 > Chronic estrogen exposure affects gene expression in the rostral ventrolateral medulla of young and aging rats: Possible role in hypertension.

Chronic estrogen exposure affects gene expression in the rostral ventrolateral medulla of young and aging rats: Possible role in hypertension.

Abstract：

BACKGROUND:Chronic exposure to estradiol-17β (E2) in adult female rats increases mean arterial pressure by stimulating superoxide production in the rostral ventrolateral medulla (RVLM). However the mechanisms behind this phenomenon are unknown. We hypothesized that E2 exposure induces the gene expression of cytokines, chemokines and NADPH oxidase (Nox) in the RVLM that promotes superoxide production and aging would exacerbate this effect. METHODS:Young adult (3-4 month old) and middle-aged (6-8 month old) female Sprague Dawley rats were sham-implanted (YS and MS respectively) or implanted s.c. with slow-release E2 pellets (20 ng of E2/day for 90 days; YE and ME respectively). Blood pressure (BP) was measured during the last 3 weeks of exposure in a separate set of rats. At the end of treatment, the animals were sacrificed and RVLM was isolated from the brainstem. PCR array and Quantitative RT-PCR were performed with the tissue to quantify genes associated with hypertension and superoxide production. Superoxide dismutase (SOD) activity was also measured in the RVLM from a different set of animals. RESULTS:E2 exposure increased mean arterial pressure in both YE and ME animals. Inflammatory genes such as interleukin-1β, interleukin-6 and monocyte chemoattractant protein-1 were significantly up-regulated in the RVLM of ME treated female rats compared to YS rats, but not in YE rats. Endothelin-1 (ET-1) gene was up-regulated in the RVLM of both YE and ME rats that were exposed to E2. Furthermore, chronic E2 treatment increased the mRNA levels of Nox1 and Nox2 genes in the RVLM of YE but not ME animals. SOD activity was reduced in MA animals, compared to young animals. E2 treatment had no significant effect on SOD activity. CONCLUSION:Chronic E2 exposure stimulates the expression of inflammatory genes in older animals and increases the expression of Nox subunits in the RVLM of younger animals. SOD activity was reduced in older animals. This suggests increased superoxide production in younger animals, but reduced superoxide elimination in older animals. On the other hand, E2 exposure stimulates ET-1 expression in both young and aging animals. These findings suggest that hypertension caused by chronic E2 exposure may involve different molecular mediators in young and aging animals, however ET-1 and superoxide could be common mediators for both age groups.

journal_name

Brain Res

journal_title

Brain research

authors

Subramanian M,Hahn-Townsend C,Clark KA,MohanKumar SM,MohanKumar PS

doi

10.1016/j.brainres.2015.09.007

subject

Has Abstract

pub_date

2015-11-19 00:00:00

pages

134-42

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(15)00705-2

journal_volume

1627

pub_type

杂志文章

在线工具

Chronic estrogen exposure affects gene expression in the rostral ventrolateral medulla of young and aging rats: Possible role in hypertension.