[Effects of different patterns of hypoxia on renin angiotension system in serum and tissues of rats].

OBJECTIVE: To Investigate the influences of chronic intermittent hypoxia (CIH) and continuous hypoxia (CH) on renin angiotensin system (RAS) in serum and tissues of rats, and therefore to investigate the mechanism of CIH-induced hypertension and hypoxia induced pulmonary hypertension. METHODS: Eighteen male Sprague-Dawley (SD) rats were divided into 3 groups: CIH group, CH group and control group (UC). CIH rats were subjected to alternating cycles of hypoxia (6% ∼ 8% O(2) in N(2) for 20 ∼ 25 s) and normoxia (21% O(2) in N(2) for 2 min) every 180 s for 7 h/d. CH rats were consistently given nitrogen (oxygen concentration 8% - 12% in the cabin, 7 h/d), while the UC rats were not treated. RESULTS: Systolic blood pressure (SBP) in the CIH rats at the end of 6th week was significantly elevated compared with baseline SBP (P < 0.001), and that in the CH and the UC rats (P < 0.05). At the end of 6th week, the expression of ACE and ACE2 in the renal arteriole was significantly different (P < 0.05), and the levels of AngII in serum and kidney tissues were increased. Ang-(1-7) was decreased in the CIH rats compared with the CH and the UC rats (P < 0.05). The levels of AngII in pulmonary tissues were increased, while the levels of Ang-(1-7) were decreased in the CH rats compared with the CIH and the UC rats (P < 0.05). SBP showed a positive correlation with AngII in serum and kidney tissues, and a negative correlation with Ang-(1-7) in serum and kidney tissues. There were significant differences in arterial wall thickness, WT%, and WA% of renal arterioles and pulmonary arterioles among the 3 groups. Wall thickness of pulmonary arterioles and kidney arterioles was positively correlated with AngII in pulmonary and kidney tissues (r = 0.386, 0.414, P < 0.05), and negatively correlated with Ang-(1-7) (r = -0.401, -0.394, P < 0.05). CONCLUSION: CIH and CH showed different effects on RAS in the serum and the tissues of rats. CIH mainly affected levels of RAS in the serum, kidney tissues and renal arterioles, and was closely related with blood pressure. CH mainly affected the levels of RAS in lung tissues and pulmonary small arteries, which may be related with pulmonary, hypertension and pulmonary arterial remodeling.

[A study of the related pathways of oxidative stress in chronic intermittent hypoxia rats and the effect of N-acetylcysteine].

OBJECTIVE: To study the relation of oxidative stress with systolic blood pressure (SBP) and renin-agiotensin system (RAS) in a rat model of chronic intermittent hypoxia (CIH), and to investigate the preventive effect and mechanism of N-acetylcysteine (NAC) in CIH-induced hypertension. METHODS: Twenty-four male Sprague-Dawley (SD) rats were divided into 4 groups: CIH+NAC group (CIH1), CIH+normal saline (NS) group (CIH2), CIH control group (CIH3) and blank control group (UC). CIH rats were subjected to alternating cycles of hypoxia (6%-8% O2 in N2 for 20-25 s) and normoxia (21% O2 in N2 for 2 min) every 180 s for 7 h per day. Rats in the CIH1 group were treated with NAC (800 ml×kg(-1)×d(-1)) by intraperitoneal injection, and those in the CIH2 group were treated with NS (5 ml×kg(-1)×d(-1)). RESULTS: SBP in the CIH2 and CIH3 groups at the end of 6th week was significantly elevated compared with the baseline SBP (P<0.001) and those in the CIH1 and the UC groups (P<0.05). The expression of angiotensin-converting enzyme (ACE) and ACE2 in renal arterioles was significantly different (P<0.05), and the levels of angiotensin II (AngII) in the serum and kidney tissues, oxidation of low density lipoprotein (ox-LDL) and malondialdehyde (MDA) in the serum were increased. Ang-(1-7) and the inhibitory capability for hydroxyl free radicals in the serum were decreased significantly in CIH2 and CIH3 groups compared with CIH1 and UC (P<0.05) groups at the end of 6th week. SBP showed a positive correlation with AngII in serum and kidney tissues, but showed a negative correlation with Ang-(1-7) in serum and kidney tissues. The levels of MDS and ox-LDL in serum showed a positive correlation with AngII in serum and kidney tissues respectively, but showed a negative correlation with Ang-(1-7) in serum and kidney tissues respectively. The inhibitory capability for hydroxyl free radicals in serum showed a positive correlation with Ang-(1-7), but a negative correlation with AngII. The level of ox-LDL showed a positive correlation with MDA, but a negative correlation with the inhibitory capability for hydroxyl free radicals. There were no significant difference between CIH1 and UC groups in parameters except of SBP and AngII (P<0.05). All the data were not different between CIH2 and CIH3 groups (P>0.05). CONCLUSIONS: CIH caused oxidative stress and RAS imbalance in rats. The imbalance of RAS in CIH rats was related with oxidative stress. The imbalance of RAS and oxidative stress may be one of the important mechanisms for CIH-induced hypertension. NAC can prevent CIH-induced hypertension through modulation of RAS by its anti-oxidative effect.