Angiotensin II enhances carotid body chemoreflex control of sympathetic outflow in chronic heart failure rabbits
Angiotensin II enhances carotid body chemoreflex control of sympathetic outflow in chronic heart failure rabbits
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DOI：
10.1016/j.cardiores.2006.03.017
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发表时间：
2006-07-01
影响因子：
10.8
通讯作者：
Schultz, Harold D.
中科院分区：
文献类型：
--
作者：
Li, Yu-Long;Xia, o-Hong Xia;Schultz, Harold D.
目的：我们研究了血管紧张素II（Ang II）是否通过颈动脉体（CB）化学感受器调节慢性心力衰竭（CHF）患者外周化学感受器反射功能。我们在静脉注射血管紧张素II之前和之后测定了肾交感神经活性（RSNA）对分级缺氧的反应（20 ng/kg/min，i.v.30min）或AT（1）受体拮抗剂（L-158，809，0.33mg/kg，i. v.）在清醒的假手术和起搏诱导的CHF兔中。我们还研究了Ang Ⅱ（100 pM）和L-158，809（1 μ M）对假手术和CHF兔离体CB化学感受器活性的影响。相反，L-158，809减弱了CHF兔RSNA中缺氧诱导的反应，但在假手术兔中没有。应用RT-PCR、Western blotting和免疫细胞化学方法，我们发现CHF兔CB中AT（1）受体的mRNA和蛋白表达均高于假手术组。与假手术组相比，慢性心力衰竭组家兔在常氧和分级缺氧时CB化学感受器传入活动增加。Ang Ⅱ可增加假手术兔CB化学感受器对缺氧的反应，但对CHF兔无明显影响。L-158，809可降低CHF兔CB化学感受器对缺氧的反应，但对假手术兔无明显影响。结论：CHF时CB中Ang Ⅱ的升高和AT（1）受体的上调可能与CB化学感受器活性增加和外周化学感受器反射功能增强有关。(c)2006年欧洲心脏病学会。出版社：Elsevier B.V版权所有。
Objectives: We investigated whether Angiotensin II (Ang II) modulates peripheral chemoreflex function through carotid body (CB) chemoreceptors in chronic heart failure (CHF).Methods: We measured renal sympathetic nerve activity (RSNA) in response to graded hypoxia before and after intravenous administration of Ang II (20ng/kg/min, i.v. 30min) or AT(1) receptor antagonist (L-158,809, 0.33mg/kg, i.v.) in conscious sham and pacing-induced CHF rabbits. We also investigated the effects of Ang II (100pM) and L-158,809 (1 mu M) on CB chemoreceptor activity in vascularly isolated-perfused CB preparations from sham and CHF rabbits.Results: Ang 11 enhanced hypoxia-induced RSNA increases in sham rabbits but not in CHF rabbits. Conversely, L-158,809 attenuated hypoxia-induced responses in RSNA in CHF rabbits but not in sham rabbits. Using RT-PCR, Western blotting, and immunocytochemistry, we found that the mRNA and protein expression of AT(1) receptor in the CB from CHF rabbits were greater than that in sham rabbits. CB chemoreceptor afferent activity during normoxia and graded hypoxia was increased in CHF rabbits compared with sham rabbits. Ang II increased the response of CB chemoreceptors to hypoxia in sham rabbits but not CHF rabbits. L-158,809 decreased CB chemoreceptor responses to hypoxia in CHF rabbits but not in sham rabbits.Conclusions: These results indicate that elevation of Ang II and concomitant upregulation of AT(1) receptor in the CB contribute to the increased CB chemoreceptor activity and enhanced peripheral chemoreflex function in CHF. (c) 2006 European Society of Cardiology. Published by Elsevier B.V All rights reserved.