肾上腺髓质素及其受体系统在自发性高血压大鼠心血管组织中的变化

Changes of adrenomedullin and its receptor system in cardiovascul tissue of spontaneously hypertensive rats

目的通过观察肾上腺髓质素(ADM)及其受体系统-降钙素受体样受体(CRLR)以及受体活性修饰蛋白(RAMPs)在自发性高血压大鼠(SHR)心血管组织中的改变,以探讨ADM在心血管系统中保护机制。方法通过放射免疫法测定SHR和WKY大鼠心肌和血管ADM含量,半定量RT-PCR测定ADM、CRLR、RAMP2和RAMP3 mRNA水平。结果SHR大鼠有显著的高血压,比对照组高76%,心脏重量与体重之比明显高于对照组46%;血浆、心肌和血管ADM含量分别较对照组高42.5%、68.3%和80.4%;ADM、CRLR、RAMP2和RAMP3 mRNA在心肌组织分别较对照组高46%、62%、41%和54%(P<0.01),而在血管组织高72%、87%、53%和74%(P<0.01)。结论SHR大鼠心血管组织ADM生成增加,ADM、CRLR和RAMP2,3基因表达亦有不同程度的增加。提示ADM及其受体系统可能在自发性高血压中发挥重要的作用。

Objective：To illustrate the protective mechanism of ADM on the cardiovascular system by observing the changes in level of ADM and its receptor system - calcitonin receptor-like receptor （CRLR） and receptor-activity-modifying proteins （RAMPs） -in myocardia and aortas of spontaneously hypertensive rats （SHRs）. Methods： The ADM content in myocardia and aortas were measured in SHRs and male Wistar Kyoto （WKY） rats （11-week-old） by radioimmunoassay （RIA）. The mRNA levels of ADM, CRLR, RAMP2 and RAMP3 were determined by semi-quantitative RT-PCR. Results： SHRs had severe hypertension, and the tail-blood pressure was 76 % higher, the ratio of heart weight to body weight （heart coefficient） 46%. higher （all P〈0. 01）. The ADM content in plasma, myocardia and aortas of SHRs increased by 42.5%, 68.3% and 80.4%, respectively （all P〈0. 01） compared with WKY rats. Furthermore, the mRNA level of ADM, CRLR, RAMP2 and RAMPs was elevated by 46 %, 62%, 41% and 54% （all P〈0. 01）, in myocardia and by 72%, 87%, 53% and 74% （all P〈0. 01）in aortas. Conclusions： In SHRs, the level of ADM was increased in myocardia and aortas, the gene expression of ADM, CRLR, RAMP2 and RAMP~ was up-regulated, and the response to ADM was potentiated. The results suggest that the changes in cardiovascular-tissue ADM and its receptor system might play an important role in the pathogenesis of hypertension