Combined, but not individual, blockade of ASIC3, P2X, and EP4 receptors attenuates the exercise pressor reflex in rats with freely perfused hindlimb muscles.

Combined, but not individual, blockade of ASIC3, P2X, and EP4 receptors attenuates the exercise pressor reflex in rats with freely perfused hindlimb muscles.
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联合而非单独阻断 ASIC3、P2X 和 EP4 受体会减弱后肢肌肉自由灌注的大鼠的运动升压反射。

DOI:
10.1152/japplphysiol.00630.2015
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发表时间:
2015
期刊:
Journal of applied physiology (Bethesda, Md. : 1985)
影响因子:
--
通讯作者:
Kaufman,MarcP
Kaufman,MarcP
中科院分区:
--
文献类型:
--
作者:
Stone,AudreyJ;Copp,StevenW;Kim,JoyceS;Kaufman,MarcP

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在健康的人体中,关于乳酸、前列腺素E_2或三磷酸腺苷在运动升压反射中起作用的假设的测试被证明是有争议的。在人类身上的发现与我们在去大脑大鼠身上的发现相似,即单独阻断乳酸、前列腺素E_2和三磷酸腺苷的受体对运动加压反射的影响很小,前提是肌肉自由灌流。人类和大鼠之间的这种相似性促使我们测试了一种假设,即在自由灌流肌肉的大鼠中,需要联合受体阻滞剂来减弱运动加压反射。我们首先比较了去大脑大鼠后肢动脉注射P2X受体拮抗剂PPADS(10 mg/kg)、激活酸敏感离子通道3通道拮抗剂APETx2(100μg/kg)或EP4受体拮抗剂L161982(2μg/kg)前后的反射。然后,我们研究了联合阻断P2X受体、ASIC3通道和EP4受体对运动加压反射的影响,使用与单独阻断相同的剂量、动脉内途径和时间进程的拮抗剂。我们发现PPADS(n=5)、APETx2(n=6)和L161982(n=6)都不能减弱反射。相反,联合阻断这些受体(n=7)可减弱反射的峰值(↓27%,P<0.019)和整合(↓48%,P<0.004)升压成分。静脉注射复合阻滞剂对反射无影响。我们的结论是,需要联合阻断细纤维肌肉传入末梢的P2X受体、ASIC3通道和EP4受体,以减弱自由灌流后肢大鼠的运动加压反射。
In healthy humans, tests of the hypothesis that lactic acid, PGE2, or ATP plays a role in evoking the exercise pressor reflex proved controversial. The findings in humans resembled ours in decerebrate rats that individual blockade of the receptors to lactic acid, PGE2, and ATP had only small effects on the exercise pressor reflex provided that the muscles were freely perfused. This similarity between humans and rats prompted us to test the hypothesis that in rats with freely perfused muscles combined receptor blockade is required to attenuate the exercise pressor reflex. We first compared the reflex before and after injecting either PPADS (10 mg/kg), a P2X receptor antagonist, APETx2 (100 μg/kg), an activating acid-sensing ion channel 3 (ASIC) channel antagonist, or L161982 (2 μg/kg), an EP4 receptor antagonist, into the arterial supply of the hindlimb of decerebrated rats. We then examined the effects of combined blockade of P2X receptors, ASIC3 channels, and EP4 receptors on the exercise pressor reflex using the same doses, intra-arterial route, and time course of antagonist injections as those used for individual blockade. We found that neither PPADS (n= 5), APETx2 (n= 6), nor L161982 (n= 6) attenuated the reflex. In contrast, combined blockade of these receptors (n= 7) attenuated the peak (↓27%,P< 0.019) and integrated (↓48%,P< 0.004) pressor components of the reflex. Combined blockade injected intravenously had no effect on the reflex. We conclude that combined blockade of P2X receptors, ASIC3 channels, and EP4 receptors on the endings of thin fiber muscle afferents is required to attenuate the exercise pressor reflex in rats with freely perfused hindlimbs.
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