Tan Jian-Xin, Chen Xin-Min, Fang Xin, Tao Meng-Jie, Huang Xiu-Lan
Department of Pediatrics, Clinical Division, Fuzhou General Hospital of Nanjing Command, Fuzhou 350025, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2008 Jun;28(6):1052-5.
To observe the effects of continuous subcutaneous adenosine infusion on pulmonary hypertension in chronically hypoxic rats.
Twenty-four SD rats were randomized into normoxic group, hypoxic group and adenosine-treated hypoxic group. Hypoxic environment was simulated in a chamber filled with 10% oxygen and 90% nitrogen. After 7 days of hypoxia, adenosine were administered subcutaneously in the rats in adenosine-treated group at the rate of 100 microg kg(-1) min(-1) via an Alzet micro-osmotic pump for 14 days, while the pumps in the other two groups contained normal saline. After 21 days of hypoxia, pulmonary artery pressure and tail-cuff blood pressure were measured, with the plasma rennin activity (RA), angiotensin II (AngII), endothelin (ET)-1, and nitric oxide (NO) determined. Inducible nitric oxide synthase (iNOS) expression in the pulmonary artery of the rats was detected using immunohistochemical method.
The mean pulmonary artery pressure (mPAP) was significantly higher in the hypoxic group than that in the normoxic group (P<0.01) and in the adenosine-treated group (P<0.01). Plasma ET-1 was significantly higher but plasma NO significantly lower in the hypoxic group than in the normoxic group (P<0.01) and the adenosine-treated group (P<0.01). iNOS expression in the pulmonary artery was higher in the hypoxic group than in normoxic group (P<0.01), and adenosine significantly increased iNOS expression in comparison with the normoxic and hypoxic groups (P<0.01). Plasma RA and AngII in the hypoxic group were significantly higher than those in the normoxic group (P<0.01) and the adenosine-treated (P<0.01).
Adenosine administered by continuous subcutaneous infusion alleviates chronically hypoxia-induced pulmonary hypertension in rats, in which rennin angiotensin system, ET-1, and iNOS/NO play a role.
观察持续皮下输注腺苷对慢性低氧大鼠肺动脉高压的影响。
将24只SD大鼠随机分为常氧组、低氧组和腺苷处理低氧组。在充满10%氧气和90%氮气的舱内模拟低氧环境。低氧7天后,腺苷处理组大鼠通过Alzet微量渗透泵以100μg·kg⁻¹·min⁻¹的速率皮下给予腺苷,持续14天,而其他两组的泵内含有生理盐水。低氧21天后,测量肺动脉压和尾袖血压,测定血浆肾素活性(RA)、血管紧张素II(AngII)、内皮素(ET)-1和一氧化氮(NO)。采用免疫组织化学方法检测大鼠肺动脉中诱导型一氧化氮合酶(iNOS)的表达。
低氧组的平均肺动脉压(mPAP)显著高于常氧组(P<0.01)和腺苷处理组(P<0.01)。低氧组血浆ET-1显著高于常氧组(P<0.01)和腺苷处理组(P<0.01),而血浆NO显著低于常氧组(P<0.01)和腺苷处理组(P<0.01)。低氧组肺动脉中iNOS表达高于常氧组(P<0.01),与常氧组和低氧组相比,腺苷显著增加iNOS表达(P<0.01)。低氧组血浆RA和AngII显著高于常氧组(P<0.01)和腺苷处理组(P<0.01)。
持续皮下输注腺苷可减轻大鼠慢性低氧诱导的肺动脉高压,其中肾素血管紧张素系统、ET-1和iNOS/NO发挥作用。