Role of anandamide transporter in regulating calcitonin gene-related peptide production and blood pressure in hypertension
Role of anandamide transporter in regulating calcitonin gene-related peptide production and blood pressure in hypertension
复制标题
花生四烯酸乙醇胺转运蛋白在调节高血压降钙素基因相关肽产生和血压中的作用
DOI：
10.1097/hjh.0b013e328329bbd7
复制
发表时间：
2009-06-01
影响因子：
4.9
通讯作者：
Li, Yuan-Jian
中科院分区：
文献类型：
--
作者：
Li, Dai;Chen, Ben-Mei;Li, Yuan-Jian
目的 探讨大麻素（AEA）转运蛋白在调节降钙素基因相关肽（CGRP）产生和血压中的作用。方法与结果检测原发性高血压患者、自发性高血压大鼠(SHRs)、2肾1夹高血压大鼠血浆AEA、CGRP、不对称二甲基精氨酸(ADMA)、一氧化氮水平以及大鼠背根神经节CGRP mRNA表达量。分离外周血淋巴细胞以检查AEA转运蛋白活性、AEA转运蛋白在调节CGRP mRNA表达中的作用或外源ADMA对AEA转运蛋白活性的影响。在高血压患者和 SHR 中，AEA 的血浆水平均升高，但 AEA 转运蛋白活性随着 CGRP 产生的减少而减弱。此外，SHR 中血浆 ADMA 水平升高，同时一氧化氮水平降低。相比之下，2肾1夹高血压大鼠血浆AEA水平升高并伴随CGRP产生增加，而血浆ADMA、一氧化氮和AEA转运蛋白活性水平没有显着变化。在体外，外源给予 AEA 上调淋巴细胞中 CGRP mRNA 的表达，该表达被 AEA 转运蛋白阻断剂 AM404 抑制，并且 AEA 转运蛋白活性被 ADMA 降低。结论 原发性高血压或SHRs患者血浆CGRP水平降低可能是由于AEA转运蛋白活性降低所致，而ADMA水平升高可能是AEA转运蛋白活性降低的原因。
Objectives To explore the role of anandamide (AEA) transporter in regulating calcitonin gene-related peptide (CGRP) production and blood pressure. Methods and results Plasma levels of AEA, CGRP, asymmetric dimethylarginine (ADMA) and nitric oxide in patients with essential hypertension, spontaneously hypertensive rats (SHRs) and 2 kidney 1 clip hypertensive rats and the CGRP mRNA expression in dorsal root ganglion of rats were measured. Peripheral blood lymphocytes were isolated to examine the AEA transporter activity, the role of AEA transporter in regulating CGRP mRNA expression or the effect of exogenous ADMA on AEA transporter activity. In both hypertensive patients and SHRs, the plasma level of AEA was elevated, but the AEA transporter activity was attenuated concomitantly with decreased CGRP production. Moreover, plasma ADMA level in SHRs was elevated accompanied by decreased nitric oxide level. By contrast, the plasma AEA level was elevated accompanied by increased CGRP production in 2 kidney 1 clip hypertensive rats, and there were no significant changes in plasma levels of ADMA, nitric oxide and the AEA transporter activity. In vitro, exogenous administration of AEA upregulated CGRP mRNA expression in lymphocytes, which was inhibited by AEA transporter blocker, AM404, and the AEA transporter activity was reduced by ADMA. Conclusion Decreased plasma CGRP level in patients with essential hypertension or SHRs is likely due to the reduced AEA transporter activity, and the increased ADMA level may account for the reduced AEA transporter activity.