摘要
目的:观察慢性间歇低氧诱发大鼠高血压发病过程中一氧化氮(NO)和一氧化氮合酶(NOS)的动态变化,探讨慢性间歇低氧诱发高血压的发病机制.方法:将Wistar大鼠(72只)随机分为间歇低氧组(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60 s,使舱内最低氧浓度达4%～6%,然后恢复至21%,8 h/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8、22、43天时各组大鼠血压、血浆NO水平和NOS活性以及不同组织内皮型一氧化氮合酶(eNOS)mRNA的表达.结果:第43天时IH组大鼠平均动脉压(MAP)较实验前升高约8 mmHg[(1 mmHg=0.133 kPa)(P<0.01)],而两对照组大鼠MAP无显著变化.IH组大鼠血浆NO水平和NOS活性随间歇低氧时间的延长逐渐下降,NO水平从第22天[(31.9±9.3)μmol/L]开始显著低于SC[(49.4±10.3)μmol/L]和UC组[(47.8±11.5)μmol/L](P均<0.01),NOS活性也从第22天[(18.1±4.5)U/ml]开始显著低于SC[(22.5±4.0)U/ml](P<0.05)和UC组[(25.6±4.0)U/ml](P<0.01),并且血浆NO水平和NOS活性与MAP均呈负相关(r=-0.566,P＜0.01和r=-0.454,P<0.05);其主动脉、心脏和肾皮质eNOS mRNA的表达在第43天时均显著低于两对照组水平(均P<0.05).SC组与UC组大鼠比较,各项观察指标差异均无统计学意义(P＞0.05).结论:慢性间歇低氧可引起eNOS表达下降和NOS活性降低,使NO合成释放减少,可能是慢性间歇低氧诱发高血压的重要原因之一.
Objective：To observe the change of nitric oxide （NO） and nitric oxide synthase （NOS） during the development of chronic intermittent hypoxia（CIHO）-induced hypertension in rats, and to evaluate their role in the mechanism of CIHO-induced hypertension. Method：Seventy two male Wister rats were divided into three groups： intermittent hypoxia group（IH）, sham control group（SC） and unhandled control group（UC）. Using 30 s infusions of nitrogen and followed by 30 s infusions of compressed air into exposure chambers （4%-6% nadir ambient oxygen with return to 21%）, IH rats were subjected to intermittent hypoxia every 60 s for 8 h/day during the diurnal sleep period; SC rats were similarly handled but received compressed air instead of nitrogen and UC rats remained unhandled. Mean arterial pressure（MAP）, the levels of NO and NOS activity in plasma as well as the expression of endothelial NOS（eNOS） mRNA in tissue were observed on day 8, 22 and 43 after experiment. Result= The IH rats showed a 8 mmHg increase in MAP （ P〈0.01） on day 43, and no significant changes of MAP were found in two controls. Plasma NO levels and NOS activity in IH rats decreased gradually over time. NO levels be gan to decrease significantly on day 22[（31.9±9.3）μmol/L] compared with that in SCE（49.4±10.3） μmol/L] and UC rats[（47.8±11.5）μmol/L]（both P 〈0.01）, and NOS activity also began to decrease significantly on day 22[（18. 1±4.5）U/ml] compared with that in SC[（22.5±4.0）U/ml]（ P 〈0.05） and UC rats[（25.6±4.0）U/ ml]（ P 〈0.01）. The Plasma NO levels and NOS activity in IH rats showed significant negative correlation with MAP （ r = -0. 566, P =0. 004 and r =-0. 454, P =0. 026 respectively）. The levels of eNOS mRNA in tissue of heart, renal cortex and aorta in IH rats were significantly decreased on day 43 compared with that in two con trois（all P 〈0.05）. All indexes were not different between SC and UC rats at any time polnt（all P 〉0.05）. Conclusion：CIHO can cause both eNOS mRNA expression and NOS activity decrease, and subsequent endothelial NO release decrease, which suggests that suppressed NO system might play an important role in the pathogenesis of CIHO-induced hypertension.
出处
《临床心血管病杂志》
CAS
CSCD
北大核心
2005年第8期472-475,共4页
Journal of Clinical Cardiology
基金
天津市自然科学基金项目(No:033611311)
