Received 2002-01-03 Accepted 2002-01-30

State Major Basic Research Development Program supported this work (No.G2000056905).

*Corresponding author. Tel: +86-10-66176255; Fax: +86-10-66176255. E-mail: tangchaoshu@263.net

生理学报, Aug. 2002, 54 (4): 337~341

Acta Physiologica Sinica

研究论文

左旋硝基精氨酸诱导的高血压大鼠心肌和血管的肾上腺髓质素与受体活性修饰蛋白2表达的变化

齐永芬1,２, 石彦荣1, 卜定方1, 蒋宏峰2, 高 霖2, 庞永正1, 唐朝枢1,2,*

1北京大学第一医院心血管病研究所, 北京 100034; 2 北京大学医学部生理系, 北京 100083

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 (receptor activity-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<0.0 5)。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。

关键词: 高血压大鼠; 肾上腺髓质素; 受体活性修饰蛋白2; mRNA

学科分类号: Q57; Q291; R544.1

Changes in adrenomedullin and receptor activity-modifying protein 2 mRNA in myocardium and vessels during L-NNA-induced hypertension in rats

QI Yong-Fen1,２, SHI Yan-Rong1, BU Ding-Fang1, JIANG Hong-Feng2, GAO Lin2, PANG Yong-Zheng1, TANG Chao-Shu1,2,*

1Institute of Cardiovascular Research, the First Hospital, Peking University, Beijing 100034; 2Department of Physiology, Health Science Center, Peking University, Beijing 100083

Abstract: 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 radioimmunoassay (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 the 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 ves- 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.

Key words: hypertensive rat; adrenomedullin; receptor activity-modifying protein 2; mRNA