Systematic understanding of acute effects of intravenous guanfacine on rat carotid sinus baroreflex-mediated sympathetic arterial pressure regulation

Systematic understanding of acute effects of intravenous guanfacine on rat carotid sinus baroreflex-mediated sympathetic arterial pressure regulation
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DOI:
10.1016/j.lfs.2016.02.051
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发表时间:
2016-03-15
期刊:
影响因子:
6.1
通讯作者:
Sugimachi, Masaru
Sugimachi, Masaru
中科院分区:
医学2区
文献类型:
--
作者:
Kawada, Toru;Shimizu, Shuji;Sugimachi, Masaru

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目的:为了评估静脉注射胍法辛(一种α(2A)-肾上腺素能激动剂)对交感神经流出中枢神经系统和交感动脉压(AP)反应的急性影响,主要方法:在麻醉的Wistar京都大鼠中,分离颈动脉窦压力感受器区域。在高剂量的静脉给药之前和之后,检查了交感神经电活动(SNA)和AP对压力感受器压力输入的反应的变化(100 μ g/kg,n=7)或低剂量(20微克/公斤,n=5)的胍法辛。较高剂量的胍法辛显著缩小了AP反应的范围(86.8 +/- 6.4至38.4 +/- 12.9 mm Hg,P < 0.01),但增加了最小AP(79.3 +/- 7.5至93.2 +/- 8.7 mm Hg,P < 0.05)。在神经弧中,胍法辛降低了反应范围(90.4 +/- 2.3至33.4 +/-10.7%,P < 0.01)和最小SNA(11.4 +/- 1.9至2.6 +/-1.5%,P < 0.01)。在外周弧中,胍法辛增加了截距(67.6 +/- 7.1至92.8 +/- 8.5 mmHg,P < 0.01),但对斜率无显著影响。较低剂量的胍法辛减弱了对神经和外周arc.Significance的影响:胍法辛抑制SNA没有显着减少AP,这可能是由于外周血管收缩作用。减少急性静脉注射胍法辛的剂量并不能帮助区分中枢交感神经抑制作用和对AP的外周血管收缩作用。(C)2016 Elsevier Inc. All rights reserved.
Aims: To assess the acute effects of intravenous guanfacine, an alpha(2A)-adrenergic agonist, on sympathetic outflow from the central nervous system and on sympathetic arterial pressure (AP) response.Main methods: In anesthetized Wistar Kyoto rats, carotid sinus baroreceptor regions were isolated. Changes in electrical sympathetic nerve activity (SNA) and AP in response to a baroreceptor pressure input were examined before and after an intravenous administration of a high dose (100 mu g/kg, n=7) or a low dose (20 mu g/kg, n=5) of guanfacine.Key findings: The higher dose of guanfacine significantly narrowed the range of the AP response (86.8 +/- 6.4 to 38.4 +/- 12.9 mm Hg, P < 0.01) but increased the minimum AP (79.3 +/- 7.5 to 93.2 +/- 8.7 mm Hg, P < 0.05). In the neural arc, guanfacine reduced both the response range (90.4 +/- 2.3 to 33.4 +/- 10.7%, P < 0.01) and the minimum SNA (11.4 +/- 1.9 to 2.6 +/- 1.5%, P < 0.01). In the peripheral arc, guanfacine increased the intercept (67.6 +/- 7.1 to 92.8 +/- 8.5 mmHg, P < 0.01) without a significant effect on the slope. The lower dose of guanfacine weakened the effects on both the neural and peripheral arcs.Significance: Guanfacine suppressed SNA without a significant reduction of AP, which may be attributable to the peripheral vasoconstrictive effect. Reducing the dose of acutely administered intravenous guanfacine does not aid in separating the central sympathoinhibitory effect from the peripheral vasoconstrictive effect on AP in anesthetized rats in vivo. (C) 2016 Elsevier Inc. All rights reserved.