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

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (1): 42-47.

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

秦旭平, 谌赟, 秦又发, 田海宏, 孙飞

南华大学药物药理研究所, 衡阳 421001, 湖南

收稿日期:2008-07-17 修回日期:2008-09-12 出版日期:2009-01-26 发布日期:2020-10-27

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

QIN Xu-ping, CHEN Yun, QIN You-fa, TIAN Hai-hong, SUN Fei

Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, Hunan, China

Received:2008-07-17 Revised:2008-09-12 Online:2009-01-26 Published:2020-10-27
About author:QIN Xu-ping, male, MD., Ph.D, majoring in preclinical and clinical study on antihypertensive drugs.E-mail:Qinxp333@hotmail.com
Supported by:
Hunan Nature Funding (05JJ30042)

摘要/Abstract

摘要： 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 (AngⅡ) 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。

关键词: 降钙素基因相关肽, 氯沙坦, 哌唑嗪, 高血压

Abstract: 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(AngⅡ) immunoactivity 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 AngⅡ 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 2K1C 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.

Key words: calcitonin gene-related peptide, losartan, prazosin, hypertension

中图分类号:

R965

秦旭平, 谌赟, 秦又发, 田海宏, 孙飞. 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[J]. 中国临床药理学与治疗学, 2009, 14(1): 42-47.

QIN Xu-ping, CHEN Yun, QIN You-fa, TIAN Hai-hong, SUN Fei. Different responses of calcitonin gene-related peptide between losartan and prazosin in early phase of renovascular hypertension[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(1): 42-47.

参考文献

[1] Kawasaki H, Takasaki K, Saitio A, et al. Calcitonin gene-related peptide acts as a novel vasodilator neurotransmitter in mesenteric resistance vessels of the rat[J]. Nature, 1988, 335(6186): 164-167.
[2] Kawasaki H, Nuki C, Saito A, et al. Adrenergic modulation of calcitonin gene-related peptide-contailing nervemediated vasodilation in the rat mesenteric resistance vessel[J].Brain Res, 1990, 506(2): 287-290.
[3] Kawasaki H, Nuki C, Saito A, et al. Role of calcitonin gene-related peptide-containing nerves in the vascular adrenergic neurotransmission[J].J Pharmacol Exp Ther,1990, 252(1): 403-409.
[4] Gangula PR, Zhao H, Supowit SC, et al. Increased blood pressure in alpha-calcitonin gene-related peptide calcitonin gene knockout mice[J].Hypertension, 2000, 35(1/2): 470-475.
[5] Kagiyama S, Varela A, Phillips MI, et al. Antisense inhibition of brain reni-angiotensin system decreased blood pressure in chronic 2-kidney, 1 clip hypertensive rats [J].Hypertension, 2001, 3 (2/2): 371-375.
[6] Kawasaki H, Takenaga M, Araki H, et al. Angiotensin inhibits neurotransmission of calcitonin gene-related peptide-containing vasodilater nerves in mesteric artery of spontaneously hypertensive rats [J].J Pharmacol Exp Ther, 1998, 284(2): 508-515.
[7] Kawasaki H.Effects of chronic administration of antihypertensive drugs on vasodilation mediated by calcitonin gene-related peptide-containing vasodilator nerves in spontaneously hypertensive rats[J].Clin Exp Pharmacol Physiol, 1992, 19(8): 569-573.
[8] Qin XP, Ye F, Liao DF, et al. Involvement of CGRP in depressor effect of losartan or perindopril in rats[J].Eur J Pharmacology, 2003, 464(1): 63-67.
[9] Peng J, Lu R, Deng HW, et al. Involvment of α-calcitonin gene-related peptide in monophoshoryl lipid A-induced delayed preconditioning in rat hearts[J].Eur J Pharmocal, 2002, 436(1 2): 89-91.
[10] Wang ZG, Liu JL, Liu Y, et al. Increased plasma vasoactive substances and antioxidant enzymes levels in prehypertensive patients[J].Zhonghua Xin Xue Guan Bing Za Zhi, 2007, 35(8): 719-22.
[11] Wang DH, Wu W, Lookingland KJ.Degeneration of capsaicin-sensitive sensory nerves leads to increase salt sensitive through enhancement of sympathoexcitatory response[J].Hypertension, 2001, 37(2/2): 440-443.
[12] Shi XY, Yang Y, Zhao YT.Plasma calcitonin gene-related peptide level in patients with essential hypertention[J]. Zhonghua Nei Ke Za Zhi, 1990, 29(10): 616-618, 639.
[13] Hobara N, Gessei-Tsutsumi N, Goda M, et al. Long-term inhibition of angiotensin prevents reduction of periarterial innervation of calcitonin gene-related peptide (CGRP)-containing nerves in spontaneously hypertensive rats[J].Hypertens Res, 2005, 28(5): 465-74.
[14] Katki KA, Supowit SC, Dipette DJ.Role of calcitonin gene-related peptide and substance P in Dahl-salt hypertension[J].Hypertension, 2001, 38(3 2): 679-682.
[15] Supowit SC, Gururaj A, Ramana CV, et al. Enhanced neuronal expression of calcitonin gene-related peptide in mineralocoricoid-salt hypertension [J].Hypertension, 1995, 25(6): 1333-1338.
[16] Supowit SC, Zhao H, Hallman DM, et al. Calcitonin gene-related peptides is a depressor of deoxycorticosteronesalt hypertension in the rat[J].Hypertension, 1997, 29(4): 945-950.
[17] Supowit SC, Zhao H, Hallman DM, et al. Calcitonin gene-related peptides is a depressor in subtotal nephrectomy hypertension in the rat[J].Hypertension, 1998, 31: 391-396.
[18] Komine N, Khang S, Wead LM, et al. Effect of combining an ACE inhibitor and an angiotensin II receptor blocker on plasma and kidney tissue angiotensin II levels[J].Am J Kidney Dis, 2002, 39(1): 159-164.