Bradykinin Contributes to Sympathetic and Pressor Responses Evoked by Activation of Skeletal Muscle Afferents P2X in Heart Failure.

Bradykinin Contributes to Sympathetic and Pressor Responses Evoked by Activation of Skeletal Muscle Afferents P2X in Heart Failure.
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DOI:
10.1159/000447906
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发表时间:
2016
期刊:
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
影响因子:
--
通讯作者:
Li J
Li J
中科院分区:
其他
文献类型:
--
作者:
Xing J;Li J

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已发表的数据表明,肌肉传入神经的嘌呤能P2X受体有助于增强交感神经活动(SNA)和血压(BP)的反应,在静态运动在心力衰竭(HF)。在本研究中,我们研究了缓激肽(BK)参与调节由P2X刺激引起的HF大鼠SNA和BP反应。我们进一步研究了BK的细胞机制。我们假设BK增强了肌肉背根神经节(DRG)神经元的P2X电流,这种作用在HF中更大,这是由于BK激肽B2和P2X3受体的上调。因此,BK放大肌肉传入P2X介导的SNA和BP反应。记录对照组和HF组大鼠肾SNA和BP反应。用Western Blot分析和膜片钳技术研究BK对HF大鼠背根神经节神经元的影响。BK注射到大鼠后肢肌动脉供血区,可增强HF大鼠由α,β-亚甲基ATP激活P2X引起的SNA和BP反射反应。此外,HF可上调大鼠背根神经节激肽B2和P2X3的蛋白表达,预先应用BK可增加HF大鼠背根神经节肌细胞α,β-亚甲基ATP诱导电流的幅度。BK在调节肌肉传入P2X参与的反射交感神经和加压反应中发挥促进作用。在HF中,由于激肽B2和P2X3受体的表达和P2X电流活性的增加,P2X反应性增强。
Published data suggest that purinergic P2X receptors of muscle afferent nerves contribute to the enhanced sympathetic nervous activity (SNA) and blood pressure (BP) responses during static exercise in heart failure (HF). In this study, we examined engagement of bradykinin (BK) in regulating responses of SNA and BP evoked by P2X stimulation in rats with HF. We further examined cellular mechanisms responsible for BK. We hypothesized that BK potentiates P2X currents of muscle dorsal root ganglion (DRG) neurons, and this effect is greater in HF due to upregulation of BK kinin B2 and P2X3 receptor. As a result, BK amplifies muscle afferents P2X-mediated SNA and BP responses. Renal SNA and BP responses were recorded in control rats and rats with HF. Western Blot analysis and patch-clamp methods were employed to examine the receptor expression and function of DRG neurons involved in the effects of BK. BK injected into the arterial blood supply of the hindlimb muscles heightened the reflex SNA and BP responses induced by P2X activation with α,β-methylene ATP to a greater degree in HF rats. In addition, HF upregulated the protein expression of kinin B2 and P2X3 in DRG and the prior application of BK increased the magnitude of α,β- methylene ATP-induced currents in muscle DRG neurons from HF rats. BK plays a facilitating role in modulating muscle afferent P2X-engaged reflex sympathetic and pressor responses. In HF, P2X responsivness is augmented due to increases in expression of kinin B2 and P2X3 receptors and P2X current activity.
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