血管紧张素Ⅱ及其受体在慢性间歇低氧诱发大鼠高血压发病过程中的动态变化

目的　观察慢性间歇低氧诱发大鼠高血压发病过程中血管紧张素Ⅱ (ATⅡ )及其受体的动态变化 ,并探讨其在慢性间歇低氧诱发高血压发病机制中的作用。方法　 72只雄性Wistar大鼠随机均分为间歇低氧组 (IH组 )、实验对照组 (SC组 )和空白对照组 (UC组 ) ;IH组大鼠循环给予氮气和压缩空气 (每一循环 6 0s,使舱内最低氧浓度达 4 %～ 6 % ,然后恢复至 2 1% ,8h/d) ,SC组大鼠循环给予压缩空气 ,UC组大鼠不予任何处理。观察第 7、2 1、4 2天时各组大鼠血压、血浆肾素活性 (RA)和ATⅡ水平以及不同组织ATⅡ 1型受体 (AT1R)mRNA的表达。结果　第 4 2天时IH组大鼠平均动脉压(MAP)为 (10 2 2± 6 2 )mmHg(1mmHg =0 133kPa) ,显著高于SC组 (95 7± 3 6 )mmHg]、UC组 (97 2±3 6 )mmHg ,P均 <0 0 5 ]和实验前水平 (94 1± 4 3)mmHg ,P <0 0 1];IH组大鼠血浆RA从第 7天(3 86± 1 2 5 )ng·ml-1·h-1]开始显著高于SC(2 73± 0 98)ng·ml-1·h-1]、UC组 (2 5 5± 0 87)ng·ml-1·h-1,P均 <0 0 5 ],血浆ATⅡ从第 2 1天 (2 14± 4 1)ng/L]开始显著高于SC(12 4± 2 1)ng/L]、UC组 (12 1± 18)ng/L ,P均 <0 0 1];并且血浆RA和ATⅡ水平与MAP均呈正相关 (r =0 5 2 9,P =0 0 0 8和r=0 4 75 ,P =0 0 19

Changes of angiotensin Ⅱ and its receptor during the development of chronic intermittent hypoxia-induced hypertension in rats

OBJECTIVE: To observe the changes of angiotensin II (ATII) and ATII type-1 receptor (AT1R) during the development of chronic intermittent hypoxia (CIHO)-induced hypertension in rats, and the effect in the mechanism of CIHO-induced hypertension. METHODS: Seventy-two male Wistar rats were divided into three groups:intermittent hypoxia group (IH), sham control group (SC) and control group (UC). By using supply of nitrogen (30 s each cycle) followed by compressed air (30 s each cycle) into the exposure chambers (4% - 6% nadir ambient oxygen with return to 21%), IH rats were subjected to intermittent hypoxia every 60 s for 8 h/d during the diurnal sleep period. SC rats were similarly treated but received compressed air instead of nitrogen. UC rats were not treated. Mean arterial pressure (MAP), the levels of ATII and renin activity (RA) in plasma as well as the expression of AT1R mRNA in tissue were measured on day 7, 21 and 42 after experiment. RESULTS: MAP was significantly elevated in IH rats (102.2 +/- 6.2) mm Hg, 1 mm Hg = 0.133 kPa] compared with initial MAP (94.1 +/- 4.3) mm Hg, P < 0.01] and compared with that in SC (95.7 +/- 3.6) mm Hg], UC (97.2 +/- 3.6) mm Hg, all P < 0.05] on day 42. The levels of ATII and RA in plasma in IH rats increased gradually over time, and RA started to increase significantly on day 7 (3.86 +/- 1.25) ng.ml(-1).h(-1)] compared with that in SC (2.73 +/- 0.98) ng.ml(-1).h(-1)], UC (2.55 +/- 0.87) ng.ml(-1).h(-1), all P < 0.05], and ATII started to increase significantly on day 21 (214 +/- 41) ng/L] compared with that in SC (124 +/- 21) ng/L], UC (121 +/- 18) ng/L, all P < 0.01]. The RA and ATII levels in plasma showed positive correlation with MAP (r = 0.529, P = 0.008; r = 0.475, P = 0.019 respectively). The expression of AT1R mRNA in heart, kidney and aorta in IH rats showed no differences compared with that in SC and UC group (all P > 0.05). All indices were not different between SC and UC rats at any time point (all P > 0.05). CONCLUSION: CIHO can cause the levels of circulating RA and ATII to increase, but has no effects on AT1R mRNA expression in tissue, which suggests that activated renin-angiotensin system may contribute to the pathogenesis of CIHO-induced hypertension.