Role of calcitonin gene-related peptide in the phenol-induced neurogenic hypertension in rats
Role of calcitonin gene-related peptide in the phenol-induced neurogenic hypertension in rats
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DOI：
10.1016/j.regpep.2004.01.011
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发表时间：
2004-07-15
影响因子：
--
通讯作者：
Li, YJ
中科院分区：
文献类型：
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作者：
Deng, PY;Ye, F;Li, YJ
以往的研究表明，辣椒素敏感的感觉神经参与了高血压的发展，在一些高血压大鼠模型。为了确定降钙素基因相关肽（CGRP;辣椒素敏感性感觉神经中的主要神经递质）在神经源性高血压大鼠模型中所起的作用，在该模型中，通过在左肾下极注射50穆尔诱导高血压，在整个实验过程中通过尾套法监测收缩压（SBP）。给药15 d后，测定平均动脉压（MAP）、血浆CGRP浓度、背根神经节（DRG）CGRP mRNA表达及脊髓I、II层CGRP含量。肾内注射苯酚后5天，SBP显著升高（164 ± 7 mm Hg，p < 0.01）。在实验结束时，与对照组相比，注射苯酚的大鼠的血压（BP）显著升高（SBP：187 +/- 6对122 +/- 4 mmHg，p < 0.01; MAP：157.56 +/- 3.02对103.80 +/- 2.04 mmHg，p < 0.01）。用辣椒素治疗，选择性地消耗辣椒素敏感神经的神经递质，未能增强肾内注射苯酚的高血压反应的发展。静脉注射特异性CGRP受体拮抗剂CGRP（8-37）也不能增加已经升高的MAP。结果表明，苯酚组大鼠脊髓后角CGRP mRNA（α-和β-CGRP亚型）表达、I、II层CGRP含量及血浆CGRP浓度均降低。这些结果表明，CGRP在苯酚诱导的高血压大鼠中不起反调节作用，并支持CGRP（α和β亚型）的减少可能有助于在这种情况下血压升高的假设。(C)2004 Elsevier B. V.保留所有权利。
Previous investigations have demonstrated that capsaicin-sensitive sensory nerves are involved in the development of hypertension in some rat models of hypertension. To determine the role played by calcitonin gene-related peptide (CGRP; the predominant neurotransmitter in capsaicin-sensitive sensory nerves) in a rat model of neurogenic hypertension, in which hypertension was induced by injecting 50 mul of 10% phenol in the lower pole of the left kidney, systolic blood pressure (SBP) was monitored by the tail-cuff method throughout the experiment. Fifteen days after injection of phenol, mean arterial pressure (MAP), concentrations of CGRP in the plasma, the expression of CGRP mRNA in dorsal root ganglia (DRG) and CGRP content in laminae I and II of the spinal cord were measured. SBP was significantly increased 5 days after the intrarenal injection of phenol (164 +/- 7 mm Hg, p < 0.01). At the end of experiment, blood pressure (BP) was significantly elevated in the phenol-injected rats compared with the controls (SBP: 187 +/- 6 vs. 122 +/- 4 min Hg, p < 0.01; MAP: 157.56 +/- 3.02 vs. 103.80 +/- 2.04 mm Hg, p < 0.01). Treatment with capsaicin, which selectively depletes neurotransmitters from the capsaicin-sensitive nerves, failed to enhance the development of hypertensive responses to the intrarenal injection of phenol. Intravenous administration of CGRP(8-37), the specific CGRP receptor antagonist, also failed to increase the already elevated MAP. The expression of CGRP mRNA (both alpha- and beta-CGRP isoforms), the content of CGRP in laminae I and II of the dorsal horn of the spinal cord and the concentration of CGRP in the plasma was decreased in the rats treated with phenol. These results suggest that CGRP does not play a counterregulatory role in the phenol-induced hypertensive rats, and support the hypothesis that reduction of CGRP (alpha and beta isoforms) could contribute to a blood pressure elevation in this setting. (C) 2004 Elsevier B.V. All rights reserved.