Abstract | BACKGROUND: OBJECTIVE: This study aimed to investigate the role of the NADPH oxidase 4 (Nox4)-induced ROS/RhoA/ROCK pathway in CIH-induced hypertension in rats. METHODS: Male Sprague-Dawley rats were exposed to CIH for 21 days (intermittent hypoxia of 21% O2 for 60 s and 5% O2 for 30 s, cyclically repeated for 8 h/day). We randomly assigned 56 male rats to groups of normoxia (RA) or vertically implemented CIH together with vehicle (CIH-V), GKT137831 (CIH-G), N-acetyl cysteine (NAC) (CIH-N), or Y27632 (CIH-Y). The rats in the RA group were continuously exposed to room air, whereas the rats in the other groups were exposed to CIH. Systolic blood pressure (BP) was monitored at the beginning of each week. After the experiment, renal sympathetic nerve activity (RSNA) was recorded, and serum and renal tissues were subjected to molecular biological and biochemical analyses. RESULTS: Compared with the BP of RA rats, the BP of CIH-V rats started to increase 2 weeks after the beginning of the experiment, subsequently stabilizing at a high level at the end of the third week. CIH increased both RSNA and oxidative stress. This response was attenuated by treatment of the rats with GKT137831 or NAC. Inhibiting Nox4 activity or ROS production reduced RhoA/ROCK expression. Treatment with Y27632 reduced both BP and RSNA in rats exposed to CIH. CONCLUSION:
Hypertension can be induced by CIH in SD rats. The CIH-induced elevation of BP is at least partially mediated via the Nox4-induced ROS/RhoA/ROCK pathway.
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Authors | Wen Lu, Jing Kang, Ke Hu, Si Tang, Xiufang Zhou, Lifang Xu, Yuanyuan Li, Shuhui Yu |
Journal | Sleep & breathing = Schlaf & Atmung
(Sleep Breath)
Vol. 21
Issue 3
Pg. 667-677
(Sep 2017)
ISSN: 1522-1709 [Electronic] Germany |
PMID | 28078487
(Publication Type: Journal Article)
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Chemical References |
- Reactive Oxygen Species
- NADPH Oxidase 4
- Nox4 protein, rat
- rho-Associated Kinases
- RhoA protein, rat
- rho GTP-Binding Proteins
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Topics |
- Animals
- Hypertension
(metabolism)
- Hypoxia
(metabolism)
- Male
- NADPH Oxidase 4
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Reactive Oxygen Species
(metabolism)
- Signal Transduction
- Sleep Apnea, Obstructive
(metabolism)
- rho GTP-Binding Proteins
(metabolism)
- rho-Associated Kinases
(metabolism)
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