肾上腺髓质素对大鼠低氧性肺动脉高压的急性降压作用及机理探讨

目的:观察肾上腺髓质素(ADM)对低氧性肺动脉高压的急性降压作用及其对体循环的影响及机理。方法:雄性Wistar大鼠分成常氧和低氧两大组,每大组分为3个剂量组。经常氧或低氧21d处理后分别经股静脉给予ADM_1-520.1nmol/kg、0.3nmol/kg、1nmol/kg,观察用药前后体循环和肺循环血流动力学的变化情况。雄性Wistar大鼠分成常氧和低氧两组,经股静脉给予ADM_1-520.3nmol/kg,观察用药前后肺循环压、体循环压变化,放免法测定血浆环磷酸腺苷(cAMP)的动态变化。结果:低氧与常氧大鼠经ADM注射后除常氧ADM_1-520.1nmol/kg注射组外肺动脉平均压(mPAP)均有不同程度的降低,低氧性肺动脉高压大鼠组更为明显(P＜0.05),持续时间更长;两组大鼠mPAP对不同剂量ADM呈不同降压效应,低氧组在0.1-0.3nmol/kg间mPAP下降与剂量成正比(P＜0.05),剂量递增至0.3nmol/kg后,mPAP下降趋势减弱,ADM_1-520.1nmol/kg注射下常氧组mPAP无明显降低,在0.3-1.0nmol/kgmPAP显著降低,并随ADM剂量增加进一步降低;两组大鼠体循环平均压(mSBP)均下降(P＜0.01),且与剂量成依赖关系,其中常氧组更显著。静脉注射ADM_1-520.3nmol/kg后血浆cAMP显著增高。结论:ADM对大鼠低氧性肺动脉高压有急性降压作用,其作用方式至少部分通过cAMP途径。

The acute inhibitory effect of adrenomedullin on hypoxia-induced pulmonary hypertension in rats

AIM: The aim of this study is to investigate the acute inhibitory effects of adrenomedullin(ADM 1-52 ) on hypoxia pulmonary hypertension and its influence on systemic blood pressure. METHODS: Thirty-six male Wistar rats were divided into two groups. Eighteen were exposed to hypoxia for 21 days as hypoxic pulmonary hypertension group,and another eighteen were kept in ambient as control group. Each group were divided into three subgroups which were injected intravenously with ADM 0 1 nmol/kg, 0 3 nmol/kg, 1 nmol/kg, respectively,then hemodynamic parameters were recorded. Plasma cyclic adenosine 3,5,-monophosphate (cAMP) was measured by radioimmunoassay before,during and after injection of 0.3nmol/kg adrenomedullin(ADM 1-52 ). RESULTS: Mean pulmonary arterial pressure (mPAP)in the hypoxia and control rats treated with ADM decreased, the fall in hypoxia rats is more obviously than control( P< 0.05), ADM (0.1-0.3 nmol/kg) produced dose-related reductions in mPAP in hypoxia rats( P< 0.05). Mean systemic blood pressure(mSBP) of the rats in both groups decreased in a does-dependent manner, and it was more obvious in control rats. Plasma cAMP is higher in hypoxia group than that in control group. CONCLUSION:WTBZhe rat hypoxia pulmonary hypertension in short term through, at least partly, cAMP-dependent mechanism. KMB]