The Correlation Studies Between Oxidative Stress And RAS In CIH-rat As Well As The Interventional Effect Of N-acetylcysteine

Objective To observe the changes of MDA, ability of inhibitting hydroxyl free radical, ox-LDL,angiotensin-converting enzyme(ACE)-angiotensinⅡ(AngⅡ) and angiotensin-converting enzyme 2(ACE2)-angiotensin-(1-7)[Ang-(1-7)] during the development of chronic intermittent hypoxia(CIH) and to intervene with NAC,and probe the relativity of oxidative stress with RAS or blood pressure in CIH-rat model. and investigate the preventive effect and mechanism of NAC in CIH-induced Hypertension.Methods Twenty-four male Sprague-Dawley(SD) rats were divided into four groups:CIH+NAC group (CIH1), CIH+NS group(CIH2), CIH control group (CIH3)and control group(UC). CIH rats were subjected to alternating cycles of hypoxia (6%～8% 02 in N2 for 20s-25s) and normoxia (21% O2 in N2 for 2min) every 180 s for 7 h/d. UC rats were not treated. CIH1 rats were injected N-acetylcysteine (NAC;800 mg.kg-1.day-1, i.p.),and CIH2 rats were injected NS (4ml.kg-1.d-1, i.p).Results weight in four groups was increased to compared with initial(p <0.05 or p<0.001), CIH2 and CIH3 rats on week 6 was significantly elevated compared with initial and CIH1, UC(P<0.001); SBP in three groups of CIH-rats on week 3 was not different between groups and initial.SBP in CIH2 and CIH3 rats on week 6 was significantly elevated compared with initial SBP(P<0.001) and CIH1, UC (allP<0.05). The immunohistochemistry of ACE and ACE2 was significantly discrepancy in arteriole of kidney in CIH2 and CIH3 rats on week 6 compared with CIH1 and UC(P<0.05).The levels of AngⅡ(in Serum and kidney tissues)and MDA were increased gradually, Ang-(1-7) and ability of inhibitting hydroxyl free radical(in Serum) were decreased significantly in CIH2 and CIH3 rats on week 6 compared with CIH1 and UC (allP<0.05).SBP showed positive correlation with AngⅡin Serum and kidney tissues (r=0.399, P<0.05; r=0.379 P<0.05). and showed negative correlation with Ang-(1-7) in Serum and kidney tissues (r=-0.368, P<0.05; r=-0.351, P<0.05). The levels of MDS or ox-LDL in plasma showed positive correlation with AngⅡin Serum and kidney tissues respectively (r=0.526, P<0.01;r=0.537, P<0.01; r=0.602, P <0.01;r=0.494, P<0.01; r=0.515,P<0.01;r=0.470, P<0.01), and showed negative correlation with Ang-(1-7)in Serum and kidney tissues respectively(r=-0.627, P<0.001; r=-0.771, P<0.001; r=-0.371,P <0.05; r=-0.514, P<0.01). The levels of ability of inhibitting hydroxyl free radical in Serum showed positive correlation with SBP or Ang-(1-7) in Serum and kidney (r=-0.667, P<0.001; r=-0.527, P<0.01; r =-0.642, P<0.001), and negative correlation with AngⅡin Serum and kidney (r=0.419, P<0.05; r=0.495, P<0.01). ox-LDL showed positive or negative correlation with MDA or ability of inhibitting hydroxyl free radical (r=0.631, P<0.001; r=-0.681, P<0.001).All indices except for SBP,weight and AngⅡin Serum were not different between CIH1 and UC rats (allP>0.05). All indices were not different between CIH2 and CIH3 rats (allP>0.05).Conclusion Durative hypertension of CIH-induced was interrelated with OS and RAS imbalance in rats, The unbalance of RAS in CIH rats was closely related to oxidative stress. The unbalance of RAS and OS may be one of the important mechanisms for CIH-induced hypertension.. And NAC can prevents CIH-induced hypertension by antioxidation.