Sympathetic nerve-derived ATP regulates renal medullary vasa recta diameter via pericyte cells: a role for regulating medullary blood flow?
Sympathetic nerve-derived ATP regulates renal medullary vasa recta diameter via pericyte cells: a role for regulating medullary blood flow?
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DOI：
10.3389/fphys.2013.00307
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发表时间：
2013
影响因子：
4
通讯作者：
Peppiatt-Wildman CM
中科院分区：
文献类型：
--
作者：
Crawford C;Wildman SS;Kelly MC;Kennedy-Lydon TM;Peppiatt-Wildman CM
现在已知周细胞是血流控制的一个新颖源，能够通过其独特的形态和收缩蛋白的表达来调节毛细血管直径。以前，我们已经表明，外源ATP通过肾周细胞引起了VASA Recta的收缩，作用于多种膜结合的P2受体，对降水的vasa recta（DVR），因此可以调节髓样血流（MBF）。 MBF的调节对于适当的尿液浓度至关重要，并为这个高且可变的代谢需求的地区提供本质氧和营养。已经提出了内源性ATP的各种来源，包括响应刺激，例如机械刺激，局部酸中毒，缺氧以及暴露于各种激素的刺激，包括上皮，内皮和红细胞。先前已经显示出肾单位的广泛交感神经神经，但是报道的神经侧重于近端和远端小管，以及亨尔的上升环。我们假设交感神经是在肾周细胞上作用的ATP的附加来源，因此调节MBF。使用大鼠活肾切片模型与视频成像和共聚焦显微镜技术结合使用，我们首先在外部和内部髓质中显示出与VASA Recta Perycytes紧密相邻的交感神经。其次，我们证明了对原位（酪氨胺）的相感神经的药理刺激，引起了周围介导的血管毛的血管收缩。通过应用P2受体拮抗剂苏拉蛋白抑制。最后，周细胞的酪胺引起的血管收缩比ATP诱发的血管收缩明显小得多。交感神经可能会在肾脏髓质中提供额外的功能调节水平。现在，需要确定在哪种生理/病理生理学的情况下，肾周细胞的交感神经神经很重要。
Pericyte cells are now known to be a novel locus of blood flow control, being able to regulate capillary diameter via their unique morphology and expression of contractile proteins. We have previously shown that exogenous ATP causes constriction of vasa recta via renal pericytes, acting at a variety of membrane bound P2 receptors on descending vasa recta (DVR), and therefore may be able to regulate medullary blood flow (MBF). Regulation of MBF is essential for appropriate urine concentration and providing essential oxygen and nutrients to this region of high, and variable, metabolic demand. Various sources of endogenous ATP have been proposed, including from epithelial, endothelial, and red blood cells in response to stimuli such as mechanical stimulation, local acidosis, hypoxia, and exposure to various hormones. Extensive sympathetic innervation of the nephron has previously been shown, however the innervation reported has focused around the proximal and distal tubules, and ascending loop of Henle. We hypothesize that sympathetic nerves are an additional source of ATP acting at renal pericytes and therefore regulate MBF. Using a rat live kidney slice model in combination with video imaging and confocal microscopy techniques we firstly show sympathetic nerves in close proximity to vasa recta pericytes in both the outer and inner medulla. Secondly, we demonstrate pharmacological stimulation of sympathetic nerves in situ (by tyramine) evokes pericyte-mediated vasoconstriction of vasa recta capillaries; inhibited by the application of the P2 receptor antagonist suramin. Lastly, tyramine-evoked vasoconstriction of vasa recta by pericytes is significantly less than ATP-evoked vasoconstriction. Sympathetic innervation may provide an additional level of functional regulation in the renal medulla that is highly localized. It now needs to be determined under which physiological/pathophysiological circumstances that sympathetic innervation of renal pericytes is important.
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影响因子：
6.3
作者：
Eppel, G. A.;Ventura, S.;Evans, R. G.
通讯作者：
Evans, R. G.
影响因子：
4.2
作者：
Bumstock, Geoffrey
通讯作者：
Bumstock, Geoffrey
影响因子：
7.3
作者：
Eppel, G. A.;Ventura, S.;Evans, R. G.
通讯作者：
Evans, R. G.
影响因子：
20.1
作者：
Dickhout, JG;Mori, T;Cowley, AW
通讯作者：
Cowley, AW
影响因子：
5.5
作者：
Jans, D;Srinivas, SP;Van Driessche, W
通讯作者：
Van Driessche, W