Inhibition Of Rho-kinase Attenuates Left Ventricular Remodeling Caused By Chronic Intermittent Hypoxia In Rats Via Suppressing Myocardial Inflammation And Apoptosis

Background and objective Chronic intermittent hypoxia(CIH), the hallmark of obstructive sleep apnea syndrome(OSAS), has been reported to play a key role in the development of OSAS-associated cardiovascular diseases including cardiac remodeling. RhoA/ Rho-kinase(ROCK) pathway has also been implicated in myocardial remodeling.However, whether this signaling pathway is involved in the myocardial remodeling induced by intermittent hypoxia is not clear. The current study's purpose is to investigate the influence of fasudil, a selective ROCK inhibitor, on CIH-induced left ventricular remodeling in rats and its possible mechanisms.Methods Adult Sprague-Dawley male rats were subjected to 8 hours of intermittent hypoxia stress per day, with or without fasudil(a selective ROCK inhibitor) for 6 weeks. The morphological features of cardiomyocytes, levels of inflammatory cytokines and myocardial apoptosis, the activity of RhoA/ROCK and nuclear factor(NF)-kB p65 were determined.Results In this study, treatment with fasudil significantly improved intermittent hypoxia-induced morphological changes of myocardium in rats. Moreover, fasudil effectively inhibited the activation of RhoA/ROCK signaling pathway and the activity of NF-?B, which was also accompanied by reduced NF-?B downstream inflammatory genes and down-regulated myocardial apoptosis.Conclusion These results suggest that fasudil attenuates LV remodeling in CIH rats, at least partly by suppressing activation of NF-?B and inflammatory reactions mediated by NF-?B and apoptosis. Inhibition of the RhoA/ROCK pathway could become an important therapeutic target in the prevention of OSAS-related cardiomyopathy.