摘要
探讨高血压大鼠心肌和血管的肾上腺髓质素(adrenomedullin,ADM)与受体活性修饰蛋白2(receptoractivity-modifying protein 2,RAMP2)mRNA的变化。用一氧化氮合酶(NOS)竞争性抑制剂左旋硝基精氨酸(L-NNA)阻断NOS制备大鼠高血压模型。用放射免疫分析方法测定血浆、心肌和血管ADM含量,及竞争性定量RT-PCR方法测定心肌和血管ADM mRNA与RAMP2 mRNA含量。结果表明,NOS阻断剂L-NNA应用4周后动物血压明显升高、心肌肥厚。心重(mg)/体重(g)比值增加35.5%(P<0.01)。血浆、心肌和血管的ADM-ir较对照组分别增加80%、72%和57%(均P<0.01)。高血压大鼠心肌和血管ADM mRNA含量显著增加,分别较正常大鼠高50%(P<0.05)和102.9%(P<0.05)。高血压大鼠心肌和血管的RAMP2 mRNA含量均显著增加,分别较正常大鼠高132%(P<0.01)和87%(P<0.01)。高血压大鼠心肌和血管ADM的升高与RAMP2的升高程度呈明显的正相关,其相关系数分别为0.741和0.885。上述观察结果表明,高血压时血浆、心肌和血管ADM水平升高,心肌和血管ADM与RAMP2基因表达上调,提示ADM/RAMP2系统在高血压发病中可能具有重要作用。
To explore the changes in adrenomedullin (ADM) and receptor activity-modifying protein 2 (RAMP2) mRNA in myocardium and vessels in hypertension, a hypertensive rat model was prepared by administering L-NNA. Contents of ADM in plasma, myocardium and vessels were measured by radioim-munoassay (RIA). The levels of pro-ADM mRNA of myocardium and vessels were determined by competitive quantitative RT-PCR. The results showed that L-NNA induced hypertension and cardiomegaly. The ratio of heart to body weight increased by 35. 5% (P <0. 01). In hypertensive rats die ir-ADM in plasma, myocardium and vessels was increased by 80% , 72% and 57% (P <0. 01) , respectively compared with the control. The amounts of ADM mRNA in myocardium and vessels were increased by 50% and 109. 2% (P <0. 05) , respectively, and the amounts of RAMP2 mRNA was increased by 132% and 87% (P<0. 01) , respectively, compared with control. The levels of ADM in myocardium and vessels were positively correlated with RAMP2 mRNA, the correlation coenficients were 0. 741 and 0. 885 (P < 0. 01) , respectively. The results obtained indicate that in hypertensive rats, ADM is elevated in plasma,myocardium and vessel, and ADM and RAMP2 mRNA are up-regulated in myocardium and vessel. The ADM/RAMP2 system may play an important role in the pathogenesis of hypertension.
出处
《生理学报》
CAS
CSCD
北大核心
2002年第4期337-341,共5页
Acta Physiologica Sinica
基金
State Major Basic Research Development Program supported this work (No. G2000056905).