Vascular reactivity to calcitonin gene-related peptide is enhanced in subtotal nephrectomy-salt induced hypertension
Vascular reactivity to calcitonin gene-related peptide is enhanced in subtotal nephrectomy-salt induced hypertension
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DOI：
10.1152/ajpheart.00598.2009
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发表时间：
2011-09-01
影响因子：
4.8
通讯作者：
DiPette, Donald J.
中科院分区：
文献类型：
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作者：
Supowit, Scott C.;Katki, Khurshed A.;DiPette, Donald J.
Supowit SC、Katki KA、Hein TW、Gupta P、Kuo L、Dickerson IM、DiPette DJ。在肾次全切除术-盐诱导的高血压中，血管对降钙素基因相关肽的反应性增强。 Am J Physiol Heart Circ Physiol 301：H683-H688，2011。首次发表于 2011 年 6 月 10 日； doi:10.1152/ajpheart.00598.2009.-在肾次全切除术 (SN) 和盐诱发的高血压中，降钙素基因相关肽 (CGRP) 在神经元合成和释放该肽不增加的情况下发挥代偿作用，减弱血压升高。因此，本研究的目的是确定这种抗高血压活性的机制是否是通过增强脉管系统对这种神经肽扩张作用的敏感性。通过SN和1％盐水饮用水诱导Sprague-Dawley大鼠高血压。对照大鼠进行假手术并饮用自来水。 11天后，大鼠通过手术放置静脉（给药）和动脉（连续平均动脉压记录）导管，并在清醒、不受约束的状态下进行研究。与对照组 (128 +/- 3 mmHg) 相比，SN-盐大鼠的基线平均动脉压 (157 +/- 5 mmHg) 较高。与对照组相比，施用 CGRP（和肾上腺髓质素）使 SN-盐大鼠的平均动脉压出现显着更大的剂量依赖性下降（低剂量和高剂量均类似 2.0 倍）。有趣的是，与对照组相比，SN-盐大鼠的分离肠系膜上动脉对 CGRP（但不是腺髓质素）的扩张作用的反应显着更高（pEC（50），SN-盐，14.0 +/- 0.1 与对照，12.0 +/- 0.1）。对CGRP受体蛋白的分析表明，在SN-盐大鼠的小动脉中，只有受体成分蛋白显着增加。这些数据表明，CGRP 的代偿性抗高血压作用是由于血管系统对该肽的扩张剂活性的敏感性增加所致。该机制可能是通过受体成分蛋白的上调，从而提供受体与信号转导途径的更有效的偶联。
Supowit SC, Katki KA, Hein TW, Gupta P, Kuo L, Dickerson IM, DiPette DJ. Vascular reactivity to calcitonin gene-related peptide is enhanced in subtotal nephrectomy-salt induced hypertension. Am J Physiol Heart Circ Physiol 301: H683-H688, 2011. First published June 10, 2011; doi:10.1152/ajpheart.00598.2009.-In subtotal nephrectomy (SN)- and salt-induced hypertension, calcitonin gene-related peptide (CGRP) plays a compensatory role to attenuate the blood pressure increase in the absence of an increase in the neuronal synthesis and release of this peptide. Therefore, the purpose of this study was to determine whether the mechanism of this antihypertensive activity is through enhanced sensitivity of the vasculature to the dilator actions of this neuropeptide. Hypertension was induced in Sprague-Dawley rats by SN and 1% saline drinking water. Control rats were sham-operated and given tap water to drink. After 11 days, rats had intravenous (drug administration) and arterial (continuous mean arterial pressure recording) catheters surgically placed and were studied in a conscious unrestrained state. Baseline mean arterial pressure was higher in the SN-salt rats (157 +/- 5 mmHg) compared with controls (128 +/- 3 mmHg). Administration of CGRP (and adrenomedullin) produced a significantly greater dose-dependent decrease in mean arterial pressure in SN-salt rats compared with controls (similar to 2.0-fold for both the low and high doses). Interestingly, isolated superior mesenteric arterioles from SN-salt rats were significantly more responsive to the dilator effects of CGRP (but not adenomedullin) than the controls (pEC(50), SN-salt, 14.0 +/- 0.1 vs. control, 12.0 +/- 0.1). Analysis of the CGRP receptor proteins showed that only the receptor component protein was increased significantly in arterioles from SN-salt rats. These data indicate that the compensatory antihypertensive effects of CGRP result from an increased sensitivity of the vasculature to dilator activity of this peptide. The mechanism may be via the upregulation of receptor component protein, thereby providing a more efficient coupling of the receptor to the signal transduction pathways.