Fasudil Improves Endothelial Dysfunction in Rats Exposed to Chronic Intermittent Hypoxia Through RhoA/ROCK/NFATc3 Pathway

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2018 Apr 12

PMID 29641598

Citations 9

Authors

Jie-Ru Li

Ya-Shuo Zhao

Yue Chang

Sheng-Chang Yang

Ya-Jing Guo

En-Sheng Ji

Affiliations

Soon will be listed here.

Abstract

Endothelial dysfunction is one of the main pathological changes in Obstructive sleep apnoea (OSA). The Rho kinase (ROCK) pathway is associated with endothelial dysfunction. However, the interaction between ROCK and nuclear factor of activated T cells isoform c3 (NFATc3) in the development of this pathological response under chronic intermittent hypoxia (CIH) is unclear. To simulate the OSA model, we established a moderate CIH rat model by administering the fraction of inspired O2 (FiO2) from 21% to 9%, 20 times/h, 8 h/day for 3 weeks. Fasudil (ROCK inhibitor, 8 mg/kg/d, i.p.) was administrated in the rats exposed to CIH for 3 weeks. Our results demonstrated that CIH caused significantly endothelial dysfunction, accompanying with increased ET-1 level, decreased eNOS expression and NO production, which reduced ACh-induced vascular relaxation responses. Moreover, RhoA/ROCK-2/NFATc3 expressions were up-regulated. Fasudil significantly improved CIH induced endothelial dysfunction. Data suggested that the ROCK activation is necessary for endothelial dysfunction during CIH.

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