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首页> 外文期刊>American Journal of Physiology >Acetylcholine and bradykinin trigger preconditioning in the heart through a pathway that includes Akt and NOS.
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Acetylcholine and bradykinin trigger preconditioning in the heart through a pathway that includes Akt and NOS.

机译：乙酰胆碱和缓激肽通过包括Akt和NOS的途径触发心脏的预处理。

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摘要

In the rabbit heart, bradykinin and ACh trigger preconditioning by a mechanism involving ATP-sensitive potassium channel-dependent production of reactive oxygen species (ROS). Recent evidence indicates that the pathway by which bradykinin causes ROS generation includes nitric oxide synthase (NOS) and protein kinase G (PKG). On the other hand, Akt was shown to be essential for ACh to generate ROS. This study determines whether these two G-coupled receptor agonists indeed have similar signaling targets, i.e., whether Akt is involved in bradykinin's pathway and whether NOS is involved in ACh's pathway. Isolated adult rabbit cardiomyocytes were incubated for 15 min in reduced MitoTracker red, which becomes fluorescent only after exposure to ROS. Bradykinin (400 nM) and ACh (250 microM) caused a 51.4 +/- 14.8% and 39.8 +/- 11.7% increase, respectively, in ROS production (P <0.005). Coincubation of either agonist with Akt inhibitor (20 microM) or infection of cells with an adenovirus containing dominant negative Akt abolished this increase. The NO donor S-nitroso-N-acetyl penicillamine (SNAP, 1 microM) also increased the ROS signal by 40.8 +/- 15.7%, but this increase was unaffected by Akt inhibitor (39.0 +/- 6.4%), implying that Akt is upstream of NOS. ACh-induced ROS production could be abolished by either of the NOS inhibitors Nomega-monomethyl-L-arginine monoacetate (100 microM) and L-N5-(1-iminoethyl)ornithine hydrochloride (L-NIO, 5 microM). L-NIO also blocked the anti-infarct effect of ACh (550 microM) in isolated rabbit hearts exposed to 30 min of regional ischemia. We conclude that both bradykinin and ACh trigger ROS generation by sequentially activating Akt and NOS.
机译：在兔心脏中，缓激肽和ACh通过涉及ATP敏感钾通道依赖性活性氧（ROS）产生的机制触发预处理。最近的证据表明，缓激肽引起ROS产生的途径包括一氧化氮合酶（NOS）和蛋白激酶G（PKG）。另一方面，Akt被证明对于ACh产生ROS是必不可少的。这项研究确定了这两种G偶联受体激动剂是否确实具有相似的信号传导靶标，即Akt是否参与缓激肽途径以及NOS是否参与ACh途径。将分离的成年兔心肌细胞在减少的MitoTracker红色中孵育15分钟，该红色仅在暴露于ROS后才发荧光。缓激肽（400 nM）和乙酰胆碱（250 microM）分别导致ROS产生增加51.4 +/- 14.8％和39.8 +/- 11.7％（P <0.005）。将激动剂与Akt抑制剂（20 microM）共同孵育或用含有显性负性Akt的腺病毒感染细胞即可消除这种增加。 NO供体S-亚硝基-N-乙酰青霉素胺（SNAP，1 microM）也使ROS信号增加了40.8 +/- 15.7％，但这种增加不受Akt抑制剂（39.0 +/- 6.4％）的影响，表明Akt在NOS的上游。 NOS抑制剂Nomega-monomethyl-L-精氨酸单乙酸盐（100 microM）和L-N5-（1-亚氨基乙基）鸟氨酸盐酸盐（L-NIO，5 microM）均可消除ACh诱导的ROS产生。 L-NIO还可阻断ACh（550 microM）在暴露于局部缺血30分钟的离体兔心脏中的抗梗塞作用。我们得出结论，缓激肽和ACh均可通过顺序激活Akt和NOS来触发ROS的产生。

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