Effects And Mechanisms Of Hydrogen Sulfide On Myocardial Injury Of Hypertension Rats Induced By Chronic Intermittent Hypoxia

Part One Establishment of the chronic intermittent hypoxia induced hypertension rat modelObjective To establish the chronic intermittent hypoxia(CIH)induced hypertension rat model.Methods Sprague-Dawley(SD)rats were randomly divided into two groups:a normoxia control(NC)group and a CIH group,rats in CIH group were exposed to chronic intermittent hypoxia environment for 21 days(8 hours per day).The hypoxia period last for 30s,then the inspired oxygen fraction was rapidly increased to 21%for 40s and sustained for 20s in each hypoxia/reoxygenation cycle.During the hypoxia period,rats in NC group received the gas flow treatment as the CIH group but using only compressed air.The baseline of systolic blood pressure(SBP)was measured by tail-cuff plethysmography non-invasively before the initiation of CIH,after the initiation of CIH,SBP was measured at the end of each week.Results Before the initiation of CIH,the SBP of the two groups showed no significant differences.After the initiation of CIH,the SBP was elevated and higher than the SBP in NC group in the following three weeks.However,SBP of rats in NC group among the three weeks displayed no significant differences.Conclusions SBP of rats exposed to CIH environment was significantly increased,which suggested that CIH applied in the present study could induce hypertension.Part Two The protective effect of different doses of exogenous hydrogen sulfide in chronic intermittent hypoxia-induced myocardial injuryObjective The present study was designed to explore the effect and the machanisms of exogenous hydrogen sulfide(H2S)in CIH-induced myocardial injuryMethods SD rats were randomly divided into five groups:a NCgroup,a CIH group and a CIH+ sodium hydrosulfide(NaHS,10?mol/kg/d)group,a CIH+NaHS(30?mol/kg/d)group,a CIH+NaHS(50 ?mol/kg/d)group,different doses of NaHS were administered intraperitoneally 30 minutes before exposure to CIH everyday,the blood pressure was measured at the end of each week during the period of CIH.At the end of establishing CIH model,the left ventricular function,the oxidative stress,apoptosis level,the ER stress level as well as the structure and function of the mitochondrial were measured.Results Exposure to CIH significantly aggravated left ventricular function and increased myocardial apoptosis as well as the level of oxidative stress,and the ER stress was also increased in CIH group compared to NC group.Exposure to CIH also damaged the mitochondrial structure and function.While treatment with NaHS improved myocardial dysfunction as well as the mitochondrial damage induced by CIH,meanwhile,the level of ER stress was elevated than rats in CIH group.The effects were associated with the dose of NaHS.Conclusions These results suggested that exogenous H2S protected myocardium against CIH-induced injury through inhibiting the mitochondrial damage but without influencing ER stress.Part Three Dl-propargylglycine alleviated myocardial injury in chronic intermittent hypoxia-induced hypertension ratsObjective The present study was aimed to explore the influence of dl-propargylglycine(PAG)inhibiting the synthesis of endogenous H2S on myocardial injury in CIH-induced hypertension rats.Methods SD rats were randomly divided into a NC group,a NC+PAG(30mg/kg/d)group,a CIH group and a CIH+PAG(30mg/kg/d)group,the SBP was measured at the end of each week during the period of CIH.After establishing the CIH model in rats,left ventricular function,oxidative stress,apoptosis and the level of endoplasmic reticulum(ER)stress were detected.Meanwhile,the level of nitric oxide(NO),the expression of the proteins such as endothelial nitric oxide synthase(eNOS),inducible nitric oxide synthase(iNOS),heme oxygenase 1(HO-1),cystathionine-?-synthase(CBS)in the left ventricular myocardium were measured.Results The SBP,left ventricular function,oxidative stress,apoptosis and the level of ER stress were elevated compared to NC rats.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.However,in NC rats,PAG induced myocardial dysfunction and up-regulated oxidative stress,apoptosis and ER stress of the myocardium.With PAG administration,the NO level and the protein expression of iNOS,CBS in CIH+PAG group were elevated than that in CIH group,however,the protein expression of eNOS and HO-1 in these two groups had no significant differences.Conclusions These results suggest that PAG may protect the myocardium against CIH-induced myocardial injury through regulating of ER stress.Futhermore,the regulation of NO production as well as CBS activity may also be associated with the protection of PAG in CIH induced myocardial injury.