氯沙坦和哌唑嗪调节早期高血压大鼠体内降钙素基因相关肽反应的差异(英文)

Different responses of calcitonin gene-related peptide between losartan and prazosin in early phase of renovascular hypertension

目的:探讨高血压早期大鼠体内降钙素基因相关肽(CGRP)的变化,并观测两类降压药物,氯沙坦或哌唑嗪在降压过程中对CGRP的反应差异。方法:采用经典的两肾一夹型高血压大鼠(Goldblatt,2K1C)为研究模型,夹尾法测定大鼠清醒状态下血压,通过公式计算出平均动脉压;放射免疫法血浆内CGRP和血管紧张素II(Ang II)的含量。反转录聚合连反应(RT-PCR)测定脊髓背根神经节中CGRP mRNA的表达。结果:收缩压、平均动脉压在结扎肾动脉10 d后较对照组快速升高(P<0.01),给予氯沙坦或哌唑嗪治疗5 d后,血压明显降低(P<0.01);实验末,高血压未治疗组血浆中Ang II、CGRP浓度(P<0.01,P<0.01)和脊髓背根神经节中的CGRP mRNA的表达明显升高(P<0.05),高血压氯沙坦治疗组可进一步升高大鼠血浆中Ang II、CGRP浓度(P<0.01,P<0.01)和脊髓背根神经节中的CGRP mRNA的表达(P<0.05);但在高血压哌唑嗪治疗组大鼠血浆中Ang II变化不显著(P>0.05),但CGRP浓度和脊髓背根神经节中的CGRP mRNA的表达与未治疗组相比显著降低(P<0.05,P<0.01)。结论:在肾血管性高血压早期含CGRP感觉神经功能存在代偿性增高,氯沙坦或哌唑嗪的不同降压机制也可能与其影响体内CGRP合成和释放差异有关。

AIM： To explore the response of calcitonin gene-related peptide （CGRP） in early phase hypertension, and the effect of two kinds of antihypertensive drugs, losartan or prazosin, on the response of CGRP in the process of hypotension. METHODS： The 2-kidney, 1-clip Goldblatt （ 2k1c ） hypertensive rats were used in the present study, the blood pressure was measured by the tail-cuff method under conscious conditions, the mean artery pressure was calculated. The CGRP-like and angiotensin Ⅱ（Ang Ⅱ） immanoactivity in the plasma were measured using radioimmunoassay. The reverse-transcription polymerase chain reaction （RT-PCR） was used for the determination of the expression of CGRP mRNA in the lumbar dorsal root ganglia（DRG）. RESULTS： The systolic blood pressure （SBP） and mean artery pressure significantly increased at the tenth day after operation （ P 〈 0.01 ）. The plasma levels of CGRP and Ang Ⅱ（ P 〈 0.01, P 〈 0.01） and the expression of CGRP mRNA were significantly increased compared with those in control group （ P 〈 0.05） at the end of the experiment. Treatment with losartan significantly decreased the blood pressure and increased the plasma concentrations of Ang Ⅱ and CGRP （P〈0.01, P〈0.01） and the expression of CGRP mRNA in DRG （ P 〈 0.05）. However, treatment with prazosin caused a hypotensive effect but companied with the decrease of CGRP in plasma concentration and mRNA in the DRG （ P 〈 0.05,P 〈 0.01 ）, and did not significantly increase the plasma Ang Ⅱ（ P 〉 0.05）compared with non-treated 2KIC hypertensive rats. CONCLUSION： These results suggest that the Goldblatt 2K1C rats exhibit a compensatory action of sensory nerves. The depressor mechanism of losartan or prazosin may be related to different effects on the synthesis and release of CGRP in the 2K1C Goldblatt hypertensive rats.