Functional knockout of the TRPV1 channel has no effect on the exercise pressor reflex in rats.
Functional knockout of the TRPV1 channel has no effect on the exercise pressor reflex in rats.
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TRPV1 通道的功能性敲除对大鼠的运动升压反射没有影响。
DOI：
10.1113/jp285267
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Kaufman,MarcP
中科院分区：
文献类型：
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作者：
Anselmi,Laura;Ducrocq,GuillaumeP;Ruiz-Velasco,Victor;Stocker,SeanD;Higgins,ShannonP;Kaufman,MarcP
瞬时受体电位香草酸1（TRPV 1）通道在细纤维传入引起运动升压反射中的作用存在争议。为了阐明这一争议，我们比较了新开发的TRPV 1 +/+，TRPV 1 +/−和TRPV 1 −/−大鼠之间的运动升压反射。颈动脉注射辣椒素（0.5 μg），在TRPV 1 +/+和TRPV 1 +/−大鼠中引起显著的升压反应，但在TRPV 1 −/−大鼠中没有。在急性分离的支配腓肠肌的背根神经节神经元中，辣椒素在从TRPV 1 +/+和TRPV 1 +/−大鼠分离的神经元中引起内向电流，但在从TRPV 1 −/−大鼠分离的神经元中没有。在股动脉自由灌注或闭塞的去大脑大鼠中，通过刺激胫神经诱发反射。我们发现，无论股动脉是否通畅，三组大鼠的反射之间没有差异。例如，股动脉开放的TRPV 1 +/+、TRPV 1 +/−和TRPV 1 −/−大鼠对收缩的峰值升压反应分别为17.1 ± 7.2、18.9 ± 12.4和18.4 ± 8.6 mmHg。用泮库溴铵刺激麻痹后的胫神经对动脉压没有影响，结果表明收缩的升压反应不是由胫神经传入轴突的电刺激引起的。我们还发现，在TRPV 1 −/−大鼠中，L4和5背根神经节中酸敏感离子通道1和内过氧化物4受体的表达水平没有上调。我们的结论是，TRPV 1不需要引起大鼠的运动升压反射的收缩肌肉有一个开放或闭塞的动脉血供。关键点收缩骨骼肌产生的反射有助于动脉血压的增加，心输出量和呼吸引起的运动。反射的感觉臂包括机械感受器和代谢感受器，其中后者表明流向运动肌肉的血液不能满足其代谢需求。代谢受体上感知供需不匹配的通道的性质存在争议;有些人认为这是瞬时受体电位香草酸1（TRPV 1）通道。使用TRPV 1通道无功能的基因工程大鼠，我们已经表明，它不需要引起元反射。
AbstractThe role played by the transient receptor potential vanilloid 1 (TRPV1) channel on the thin fibre afferents evoking the exercise pressor reflex is controversial. To shed light on this controversy, we compared the exercise pressor reflex between newly developed TRPV1+/+, TRPV1+/−and TRPV1−/−rats. Carotid arterial injection of capsaicin (0.5 μg), evoked significant pressor responses in TRPV1+/+and TRPV1+/−rats, but not in TRPV1−/−rats. In acutely isolated dorsal root ganglion neurons innervating the gastrocnemius muscles, capsaicin evoked inward currents in neurons isolated from TRPV1+/+and TRPV1+/−rats but not in neurons isolated from TRPV1−/−rats. The reflex was evoked by stimulating the tibial nerve in decerebrated rats whose femoral artery was either freely perfused or occluded. We found no difference between the reflex in the three groups of rats regardless of the patency of the femoral artery. For example, the peak pressor responses to contraction in TRPV1+/+, TRPV1+/−and TRPV1−/−rats with patent femoral arteries averaged 17.1 ± 7.2, 18.9 ± 12.4 and 18.4 ± 8.6 mmHg, respectively. Stimulation of the tibial nerve after paralysis with pancuronium had no effect on arterial pressure, findings which indicated that the pressor responses to contraction were not caused by electrical stimulation of afferent tibial nerve axons. We also found that expression levels of acid‐sensing ion channel 1 and endoperoxide 4 receptor in the L4 and 5 dorsal root ganglia were not upregulated in the TRPV1−/−rats. We conclude that TRPV1 is not needed to evoke the exercise pressor reflex in rats whose contracting muscles have either a patent or an occluded arterial blood supply.Key pointsA reflex arising in contracting skeletal muscle contributes to the increases in arterial blood pressure, cardiac output and breathing evoked by exercise.The sensory arm of the reflex comprises both mechanoreceptors and metaboreceptors, of which the latter signals that blood flow to exercising muscle is not meeting its metabolic demand.The nature of the channel on the metaboreceptor sensing a mismatch between supply and demand is controversial; some believe that it is the transient receptor potential vanilloid 1 (TRPV1) channel.Using genetically engineered rats in which the TRPV1 channel is rendered non‐functional, we have shown that it is not needed to evoke the metaboreflex.