Xiufang Zhou1, Si Tang1, Ke Hu2, Zhan Zhang1, Pei Liu1, Yuchuan Luo1, Jing Kang1, Lifang Xu1. 1. Division of Respiratory Disease, Renmin Hospital of Wuhan University, Zhangzhidong Road No. 99, Wuhan, 430060, China. 2. Division of Respiratory Disease, Renmin Hospital of Wuhan University, Zhangzhidong Road No. 99, Wuhan, 430060, China. huke-rmhospital@163.com.
Abstract
BACKGROUND: Chronic intermittent hypoxia (CIH), an important basis of the pathogenesis of organ damage induced by obstructive sleep apnea syndrome (OSAS), is associated with myocardial injury, such as left ventricular dysfunction, apoptosis, and oxidative stress. Endogenous hydrogen sulfide (H2S) plays an important role in maintaining cardiovascular functions. Many studies have demonstrated that exogenous H2S has protective effects against myocardial injury induced by various cardiovascular diseases, and inhibiting the generation of endogenous H2S has opposite effects. However, the effect of DL-propargylglycine (PAG), an effective inhibitor of cystathionine γ-lyase (CSE)-synthesized H2S, on the regulation myocardial injury remains controversial. PURPOSE: The present study was aimed to explore the influence of PAG on myocardial injury induced in rats by CIH. METHODS: Sprague-Dawley rats were randomly divided into a normal control (NC) group, a CIH group, a NC + PAG group, and a CIH + PAG group. After establishing the CIH model in rats, blood pressure, left ventricular function, oxidative stress, apoptosis, and the level of endoplasmic reticulum (ER) stress were detected. RESULTS: In NC rats, PAG had no effect on blood pressure, but induced myocardial dysfunction and up-regulated oxidative stress and apoptosis of the myocardium. In the CIH + PAG group, pretreatment with PAG significantly reduced blood pressure and improved the left ventricular ejection fraction (LVEF) and the left ventricular fractional shortening (LVFS) compared to the CIH group. Significantly lower levels of oxidative stress, apoptosis, and the ER stress were detected in the CIH + PAG group than in the CIH group. CONCLUSION: These results suggest that PAG can protect the myocardium against CIH-induced injury through inhibition of endoplasmic reticulum stress.
BACKGROUND:Chronic intermittent hypoxia (CIH), an important basis of the pathogenesis of organ damage induced by obstructive sleep apnea syndrome (OSAS), is associated with myocardial injury, such as left ventricular dysfunction, apoptosis, and oxidative stress. Endogenous hydrogen sulfide (H2S) plays an important role in maintaining cardiovascular functions. Many studies have demonstrated that exogenous H2S has protective effects against myocardial injury induced by various cardiovascular diseases, and inhibiting the generation of endogenous H2S has opposite effects. However, the effect of DL-propargylglycine (PAG), an effective inhibitor of cystathionine γ-lyase (CSE)-synthesized H2S, on the regulation myocardial injury remains controversial. PURPOSE: The present study was aimed to explore the influence of PAG on myocardial injury induced in rats by CIH. METHODS:Sprague-Dawley rats were randomly divided into a normal control (NC) group, a CIH group, a NC + PAG group, and a CIH + PAG group. After establishing the CIH model in rats, blood pressure, left ventricular function, oxidative stress, apoptosis, and the level of endoplasmic reticulum (ER) stress were detected. RESULTS: In NC rats, PAG had no effect on blood pressure, but induced myocardial dysfunction and up-regulated oxidative stress and apoptosis of the myocardium. In the CIH + PAG group, pretreatment with PAG significantly reduced blood pressure and improved the left ventricular ejection fraction (LVEF) and the left ventricular fractional shortening (LVFS) compared to the CIH group. Significantly lower levels of oxidative stress, apoptosis, and the ER stress were detected in the CIH + PAG group than in the CIH group. CONCLUSION: These results suggest that PAG can protect the myocardium against CIH-induced injury through inhibition of endoplasmic reticulum stress.
Authors: Carmen M Troncoso Brindeiro; Ana Q da Silva; Kyan J Allahdadi; Victoria Youngblood; Nancy L Kanagy Journal: Am J Physiol Heart Circ Physiol Date: 2007-08-31 Impact factor: 4.733
Authors: Ling Chen; Jin Zhang; Tracey X Gan; Ye Chen-Izu; Jeffrey D Hasday; Morris Karmazyn; C William Balke; Steven M Scharf Journal: J Appl Physiol (1985) Date: 2007-11-15