[大鼠慢性间歇性缺氧诱导高血压发展过程中血管紧张素II及其受体的变化]

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

作者信息

Yuan Zhi-Ming, Chen Bao-Yuan, Wang Pei-Xian, Li Shu-Ying, Chen Yong-Li, Dong Li-Xia

机构信息

Department of Respiratory Medicine, General Hospital, Tianjin Medical University, Tianjin 300052, China.

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2004 Sep;27(9):577-80.

PMID:15498265

Abstract

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.

摘要

目的

观察大鼠慢性间歇性缺氧（CIHO）诱导高血压过程中血管紧张素II（ATII）及1型血管紧张素II受体（AT1R）的变化，以及其在CIHO诱导高血压机制中的作用。

方法

将72只雄性Wistar大鼠分为三组：间歇性缺氧组（IH）、假手术对照组（SC）和正常对照组（UC）。通过向暴露舱内供应氮气（每个周期30秒），随后供应压缩空气（每个周期30秒）（最低环境氧含量为4% - 6%，恢复至21%），IH组大鼠在白天睡眠期间每隔60秒接受间歇性缺氧处理，持续8小时/天。SC组大鼠接受类似处理，但供应的是压缩空气而非氮气。UC组大鼠不做处理。在实验第7、21和42天测量平均动脉压（MAP）、血浆中ATII水平和肾素活性（RA）以及组织中AT1R mRNA的表达。

结果

与初始MAP [（94.1±4.3）mmHg，1 mmHg = 0.133 kPa]相比，IH组大鼠在第42天MAP显著升高[（102.2±6.2）mmHg，P < 0.01]，与SC组[（95.7±3.6）mmHg]、UC组[（97.2±3.6）mmHg，P均< 0.05]相比也显著升高。IH组大鼠血浆中ATII和RA水平随时间逐渐升高，与SC组[（2.73±0.98）ng·ml⁻¹·h⁻¹]、UC组[（2.55±0.87）ng·ml⁻¹·h⁻¹，P均< 0.05]相比，RA在第7天开始显著升高[（3.86±（1.25）ng·ml⁻¹·h⁻¹]，与SC组[（124±21）ng/L]、UC组[（121±18）ng/L，P均< 0.01]相比，ATII在第21天开始显著升高[（214±41）ng/L]。血浆中RA和ATII水平与MAP呈正相关（r分别为0.529，P = ；r = 0.475，P = 0.019）。与SC组和UC组相比，IH组大鼠心脏、肾脏和主动脉中AT1R mRNA的表达无差异（P均> 0.05）。在任何时间点，SC组和UC组大鼠的所有指标均无差异（P均> 0.05）。