The Study On The Mechanism Of Intermittent Hypoxia With Different Frequencies Induced Hypertension And The Effect Of Antioxidant Tempol

ObsjectiveObstructive sleep apnea syndrome (OSAS) is a common disease of sleep disorder mainly due to chronic intermittent hypoxia (IH) caused by hypoxia-reoxygenation.A large number of epidemiologic studies indicate that there is a close link between hypertension and OSAS. However, the exact mechanism of IH-induced hypertension is still unkown. Studies have confirmed that OSAS is a oxidative stress disorders. Therefore, whether OSAS may cause vascular endothelial dysfunction and enhanced sympathetic nerve activity through oxidative stress and ultimately develop hypertension still needs further study. Therefore, wo design the different frequencies intermittent hypoxia modals of rats,to observe changs in blood pressure, serum vasoactive substances,and sympathetic nerve activity, the level of oxidative stress, and the effect of antioxidant Tempol,in order to explore the possible mechanism of hypertension induced by CIH, provide effective theoretical basis for clinical treatment of OSAS.Contents1、To study endothelial function and sympathetic activity in rats exposed to different frequencies intermittent hypoxia2、To study the effects of Tempol on endothelial dysfunction and enhanced sympathetic nerve activity with chronic intermittent hypoxia.MethodsThe first part:The paper designs the chronic intermittent hypoxia modal of rats with different frequencies of10,20,30,&40/hr, adjusted by computer-controlled device with oxygen concentration of5%.Forty male Wistar rats were randomly divided into five groups of eight each, including normoxic control group (NC)、IH10、IH20、IH30and IH40groups.The second part:adding four treatment groups (IHT1、IHT2、IHN1、 IHN2). Among the treatment groups, IHT1、IHT2groups were treated with10%Tempol100mg· kg-1· d-1by intraperitoneal injection before exposed to IH and on day 28after exposed to IH respectively, and IHN1、IHN2groups were treated with NS as control. SBP were observed every week, plasma ET-1, NO, eNOS, NE, E and MDA in plasma and adrenal gland tissues were measured after experiment.ResultsThe part one1、There was no difference in all groups of SBP in rats before experiment. With the experimental time, the SBP of rats in IH groups increased gradually, was significantly higher than the level before the experiment and NC group (P<0.05or P<0.01) in weeks6.The SBP of different frequencies IH groups were significantly different (F=9.213, P<0.05).SBP were gradually elevated with increased frequencies. The SBP of NC group was no significant difference compared with those before the experiment.2、Serum ET-1(F=22.080, P<0.01)、NO (F=19.369, P<0.01) eNOS (F=14.325, P<0.01) in different frequencies IH were significantly different, ET-1gradually increased with increased frequence.while NO、eNOS decreased. But there’s no statistics difference between IH30group and IH40group. SBP showed a positive correlation with ET-1(r=0.659, P=0.000), but showed a negative correlation with NO (r=-0.540, P=0.000)3、Serum NE(F=13.136, P <0.01) and E(F=20.877, P <0.01) in different frequencies IH were significantly different,gradually increased with increased frequence. But there’s no statistics difference between IH30group and IH40group. SBP showed a positive correlation with NE、E (r=0.542, P=0.000; r=0.540, P=0.000)The part two1、There was no difference in all groups of SBP in rats before experiment. With the experimental time, the SBP of rats in IH group and IHN1、IHN2groups increased gradually. SBP in the IHT2group were higher than the NC group (P<0.05or P0.01)、IHT1groups (P<0.05or P<0.01). No significant difference were found between IHT1group and NC group.2、Serum ET-1(F=25.681, P<0.01)、NE (F=14.769, P<0.01)、E (F=28.017, P<0.01)、NO(F=19.281, P<0.01)and eNOS (F=22.184, P<0.01) in all IH groups were significantly different. The levels of ET-1、NE、E in the two Tempol treatment groups were obviously lower than the NS groups (P<0.05or P<0.01), while NO、 eNOS was significantly higher (P<0.05or P<0.01). ET-1、NE. E in the IHT2group were higher,and NO、eNOS was significantly lower than the NC group (P<0.05)、 IHT1groups (P<0.01). No significant difference were found between IHT1group and NC group.3、Serum MDA (F=25.681, P<0.01) and MDA in the adrenal gland (F=13.649, P<0.001) in all IH groups were significantly different. The levels of MDA in the two Tempol treatment groups were obviously lower than the NS groups (P<0.05or P <0.01).Which in the IHT2group were higher than the NC group (P<0.05or P<0.01) and IHT1groups (P<0.05or P<0.01).No significant difference were found between IHT1group and NC group.Conclusion1、CIH can lead to sustained elevation of blood pressure,which suggests that CIH caused by long-term sleep apnea is a very important cause of OSAS-associated hypertension. There was a trend that Blood pressure elevated with the increased IH frequencies in a certain frequency.2、CIH can cause vascular endothelium injury and increased sympathetic nerve activity,which may be the mechanisms of CIH-induced hypertension. In a certain frequency, the higher frequence of intermittent hypoxia, the more obvious the damage of endothelium and the enhanced sympathetic nerve activity.3、CIH can generate a lot of ROS, cause systematic and local oxidative stress Antioxidant Tempol could reduce oxidative stress by scavenging superoxide.4、Tempol could prevent and alleviate endothelium injury and enhanced sympathetic nerve activity, and high blood pressure, but cannot reverse increased blood pressure completely.